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2024-03-07 22:17:37

云天化集团有限责任公司官网、云天化集团、云天化,化肥,有机化工,玻纤新材料,盐及盐化工,精细磷化工

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Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics | Cell Death & Disease

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Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics

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Published: 01 April 2021

Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics

Rongkai Shi1 na1, Shilong Ying1 na1, Yadan Li1, Liyuan Zhu

ORCID: orcid.org/0000-0001-6959-94351, Xian Wang2 & …Hongchuan Jin1 Show authors

Cell Death & Disease

volume 12, Article number: 346 (2021)

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CancerEpigenetics

AbstractN6-methyladenosine (m6A), the most prevalent and reversible modification of mRNA in mammalian cells, has recently been extensively studied in epigenetic regulation. YTH family proteins, whose YTH domain can recognize and bind m6A-containing RNA, are the main “readers” of m6A modification. YTH family proteins perform different functions to determine the metabolic fate of m6A-modified RNA. The crystal structure of the YTH domain has been completely resolved, highlighting the important roles of several conserved residues of the YTH domain in the specific recognition of m6A-modified RNAs. Upstream and downstream targets have been successively revealed in different cancer types and the role of YTH family proteins has been emphasized in m6A research. This review describes the regulation of RNAs by YTH family proteins, the structural features of the YTH domain, and the connections of YTH family proteins with human cancers.

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Facts

The effects of YTH proteins on RNA metabolism are different but overlap to some degree.

The structure of the YTH domain helps YTHDF proteins recognize and bind m6A-containing transcripts.

Structural crystallography studies have elaborated the molecular basis of YTH domains to read m6A-modified RNA.

YTH proteins have different targets in different cancers and are involved in almost every aspect of tumorigenesis and cancer progression.

Open questions

What is the precise unified model of YTH proteins in the regulation of m6A modification? Are these proteins different or redundant?

Is evaluating structural differences in YTH domains the potential direction for exploring and explaining the complex phenomena in this field?

Is a highly selective YTH domain inhibitor a potential therapeutic agent for cancer?

Is the existing structural information about the YTH domain useful for guiding the rational design of selective YTH domain inhibitors?

IntroductionSince the 1950s, nucleotides, which are the basic molecular components of RNA, have been found to undergo a number of chemical modifications on their adenosine (A), guanosine (G), cytidine (C), and uridine (U) nucleosides. Over 100 kinds of RNA modifications, such as hm5C, m1A, and m6A, have been found and these modifications can affect the biogenesis, structure, and function of RNA in different ways; these modifications have been the hotspots in epigenetics in recent years and still have great potential for exploration. N6-methyladenosine (m6A) has been considered the most prevalent and reversible modification of mRNA in eukaryotic cells since its initial discovery in the 1970s1. m6A modification is generally located in the consensus motif DRACH (D = G, A, or U; R = G or A; H = A, C, or U), which is enriched in the coding sequence (CDS) and 3′ untranslated region (3′ UTR) of RNA1,2,3,4. The regulation of m6A depends on three important factors, “writers”, “erasers”, and “readers”. “Writers” and “erasers” add and remove m6A modifications to and from RNA, respectively, while “readers” recognize m6A and affect the fate of RNA. Generally, m6A reader proteins can be divided into three classes, which use the YTH domain (YTH family proteins), m6A switch mechanism (hnRNPC, hnRNPG, and hnRNPA2B1), or common RNA-binding domain and its flanking regions (IGF2BPs and hnRNPA2B1) to bind m6A-containing transcripts5. In recent years, writers and erasers have been actively researched6, and recently, the focus has gradually turned to readers, especially YTH family proteins, due to the application of several novel methods. m6A-seq, based on antibody-mediated capture and massively parallel sequencing, helps us identify m6A sites at the transcriptome level. In addition to traditional methods such as RIP-seq, new techniques such as CLIP-seq and PAR-CLIP, based on combining immunoprecipitation with in vivo UV crosslinking enhanced by photoactivatable ribonucleosides, help us identify the targets of m6A readers7,8,9,10. These methods are shedding new light on RNA modifications. Therefore, we attempt to review the regulation of transcripts by YTH family proteins, the structural basis of the YTH domain, and the association of YTH family proteins with human cancers.YTH family proteins recognize m6A and regulate RNA processesm6A modification is regulated by RNA methyltransferase complexes—writers—and demethylases—erasers. To catalyze N6-methyladenosine (m6A) RNA methylation, methyltransferase-like 3 (METTL3) and human methyltransferase-like 14 (METTL14) form a stable heterodimer core complex with Wilms tumor 1-associated protein (WTAP), which enables the complex to localize to nuclear speckles enriched with pre-mRNA processing factors11,12. Additionally, other adaptor proteins, such as RBM15/15B, VIRMA, and ZC3H13, have been shown to be important for facilitating the function of the methyltransferase complex13,14,15. Regarding demethylases, only fat mass and obesity-associated (FTO) and AlkB homolog 5 (ALKBH5) have been found to be available to catalyze m6A demethylation thus far16,17. The YTH domain, the structural basis for the recognition and binding of m6A-modified RNA, enables a series of proteins such as YTHDF1-3 and YTHDC1-2 to act as readers in the regulation of m6A-containing transcripts. Different YTH family proteins function in different ways to influence RNA splicing, export, translation, and decay (Fig. 1).Fig. 1: Model of YTH family proteins modulating m6A-containing RNAs.In cell nucleus, “writers” and “erasers” add and remove m6A modifications to and from RNA. YTHDC1 regulates splicing and mediates the export of m6A-containing mRNAs by recruiting SRSF3, while blocking SRSF10 mRNA binding. In cytoplasm, YTHDF1 recognizes m6A-containing mRNAs and promotes its translation initiation and elongation. And the m6A-containing mRNAs can also be recognized by YTHDF2, which promotes their degradation through two pathways, CCR4-NOT complex-mediated deadenylation and HRSP12-mediated endoribonucleolytic cleavage. YTHDF3 interacts with YTHDF1 and YTHDF2 to accelerate metabolism of m6A-modified mRNAs. YTHDC2 mainly functions to regulate the switch from mitosis to meiosis by interacting with MEIOC. YTHDC2 interacts with XRN1, UPF1, and MOV10 to destabilize its target RNAs. Also, the binding of YTHDC2 to the 18S rRNA and its 3′-5′ RNA helicase activity facilitates the translation of its target RNAs.Full size imageYTHDF1-3YTHDF1 selectively recognizes m6A-modified mRNAs via the YTH domain, promotes their loading into the ribosome, and interacts with initiation factors to facilitate their translation via the N-terminal domain18. In addition to mediating translation initiation, YTHDF1 can also bind to the m6A site in the CDS of some mRNAs to assist with translation elongation19. Additionally, some research has indicated that YTHDF1 may sometimes mediate the target transcript’s stability20,21,22. It is worth mentioning that YTHDF1 is of great importance in the field of neuroscience since it was reported to be capable of inducing axon regeneration23, regulating axon guidance24, and thereby facilitating learning and memory25 by enhancing the translation of specific transcripts. Conversely, YTHDF2 selectively binds m6A-modified RNA and regulates its degradation by recruiting the CCR4-NOT complex to accelerate RNA deadenylation10,26,27. Another YTHDF2-mediated RNA degradation mechanism is endoribonucleolytic cleavage via HRSP12-mediated bridging of YTHDF2-bound RNAs to RNase P/MRP, through which a subset of circular RNAs is selectively downregulated in an m6A-dependent manner28. The P/Q/N-rich N-terminal domain of YTHDF2 is responsible for its function in RNA decay, while its aa 101–200 region interacts with the SH domain of CNOT1, and its aa 1–100 region is the HRSP12 binding region. In addition, YTHDF3 interacts with YTHDF1 to help promote protein translation, and with YTHDF2 to affect the decay of methylated mRNA transcripts29. There is also a model of m6A regulation in which pre-mRNA is first recognized by YTHDF3, which acts as an assigner, and YTHDF1 and YTHDF2 then competitively interact with YTHDF3, thus determining the fate of the mRNA transcript30. Importantly, recent studies have revealed that YTHDFs can be involved in liquid-liquid phase separation by binding multi-m6A-modified mRNA scaffolds and then forming YTHDF–m6A–mRNA complexes. These complexes then partition into phase-separated compartments such as P bodies, stress granules, or neuronal RNA granules to decide whether the mRNA should be degraded, translated, or undergo other events. Especially in stress granule formation, YTHDF proteins are critical in recruiting mRNA to stress granules. In addition, this phase separation is significantly enhanced by mRNAs that contain multiple m6A motifs. In contrast to mRNAs containing a single m6A site, mRNAs containing multiple m6A sites tend to act as scaffolds for the binding of YTHDF proteins to juxtapose their low-complexity domains and initiate phase separation31,32,33,34. Remarkably, given that YTH domain-containing proteins are m6A readers, it has also been reported that YTHDF2 and YTHDF3 can influence m6A modification levels by blocking the demethylase activity of FTO and ALKBH in different ways, for instance, in heat shock stress-induced transcripts35,36,37. However, recently, some researchers developed a fundamentally different model to explain the effect of YTHDF proteins on m6A-containing transcripts. They hypothesized that the function of YTHDF proteins is redundant and that each paralog compensates for the function of the other paralogs. More importantly, YTHDF proteins show identical binding to all m6A-containing transcripts and function together to promote the decay of these transcripts38,39,40.YTHDC1-2YTHDC1, also called YT521-B, was first found to be an RNA splicing-related protein in 1988 because of its glutamic acid/arginine-rich carboxy domain with splicing factors41. It is a ubiquitously expressed nuclear protein and localized in YT bodies adjacent to nuclear speckles42. It interacts with SAF-B and Sam68 to modulate alternative splice site selection in a concentration-dependent manner, which is regulated by tyrosine phosphorylation mediated by src kinases43. Additionally, YTHDC1 shuttles between the nucleus and the cytosol, where it is phosphorylated by SRC and TEC tyrosine kinase family members, causing its transformed function in RNA splicing44. Recently, as the ability of the YTH domain to recognize m6A has gradually been recognized, the association between YTHDC1 and m6A has been partially clarified. YTHDC1 promotes exon inclusion in m6A-modified RNA transcripts in an m6A-dependent manner by recruiting the pre-mRNA splicing factor SRSF3 while blocking SRSF10 mRNA binding to regulate splicing45. The interaction with SRSF3 helps YTHDC1 steer target mRNAs into the mRNA nuclear export pathway; thus, YTHDC1 mediates the export of m6A-containing mRNAs46. For instance, YTHDC1 mediates m6A-dependent mRNA splicing to control neuronal functions and fine-tune sex determination in Drosophila47,48. In addition to playing roles in mRNA splicing and export, YTHDC1 was recently found to regulate the stability of mRNA. YTHDC1 facilitates the decay of chromosome-associated regulatory RNAs in an m6A-dependent manner through nuclear exosome targeting-mediated nuclear degradation and thus decreases chromatin accessibility and represses gene expression49. Furthermore, YTHDC1 is involved in controlling the stability of MAT2A mRNA, which is upregulated through mRNA stabilization in response to S-adenosylmethionine depletion50. Importantly, YTHDC1 recognizes m6A residues on XIST, which is essential for XIST’s function in mediating the transcriptional silencing of genes on the X chromosome13. However, the mechanism by which YTHDC1 binding to XIST leads to gene silencing remains unclear. In addition to its function as an RNA-binding protein, YTHDC1 promotes H3K9me2 demethylation and gene expression by interacting with and recruiting KDM3B to chromatin regions51. The molecular role of the last member of the YTH family, YTHDC2, in the regulation of m6A remains uncertain. YTHDC2 was first found to be an RNA helicase with a YTH domain52. Similar to other YTH family proteins, YTHDC2 is able to recognize and bind m6A moieties in mRNA to have a regulatory role53,54. Several studies have revealed the importance of YTHDC2 in the meiosis of germline cells. YTHDC2 interacts with MEIOC, a meiosis-specific protein, and XRN1, a 5′–3′ exoribonuclease, to regulate the switch from mitosis to meiosis through posttranscriptional regulation of target transcripts54,55,56,57,58. YTHDC2 enhances the translation efficiency of its targets and decreases their mRNA abundance53. It is an RNA-induced ATPase with 3′–5′ RNA helicase activity mediated by its DEAH helicase domain54. The ankyrin repeats help YTHDC2 to interact with XRN1, UPF1, and MOV10, probably to destabilize its target RNAs53,54,59. The binding of YTHDC2 to the 18S rRNA of the small ribosomal subunit in close proximity to the mRNA entry tunnel and exit site suggests that YTHDC2 directly bridges interactions between m6A-containing mRNAs and the ribosome to promote translation59. It has also been implied that the R3H domain contributes to RNA binding by stabilizing the interaction between YTHDC2 and its m6A-containing substrates59. Interestingly, m6A residues located within the coding sequence (CDS) positively regulate translation by resolving mRNA secondary structures, for which YTHDC2 is required because of its helicase activity60. Recently, two hepatic studies also provided evidence that YTHDC2 helps decrease the stability of its target mRNAs and inhibit gene expression in an m6A-dependent manner61,62.Structural basis for the selective binding of m6A-modified RNA by YTH family proteinsAfter YT521-B was identified as an RNA splicing-related protein, a conserved region in its protein sequence that is present only in eukaryotic genomes was identified and termed the YT homology (YTH) domain63. The YTH domain has been identified in 174 different proteins of eukaryotic species and is abundant in plants. The YTH domain contains 100–150 amino acids and is characterized by 14 invariant and 19 highly conserved residues64. In addition to humans, the YTH domain has also been found in Drosophila63, fission yeast65, Saccharomyces cerevisiae66, Plasmodium falciparum67, and many species of plants68,69,70. YTH domain-containing proteins in other eukaryotic species perform many of the same or similar functions as those found in humans. For example, the m6A mRNA methylation program has been revealed in the malaria parasite, and PfYTH1 and PfYTH2, YTH domain-containing proteins in P. falciparum, were confirmed to be m6A readers67,71. In Arabidopsis, m6A recognition by the YTH domain-containing proteins ECT2, ECT3, and ECT4 are important for cell proliferation and plant organogenesis72,73. In fission yeast, Mmi1, a deeply researched YTH domain-containing protein, selectively recognizes a cis-acting region (DSR) specific for meiotic transcripts and directs them to the nuclear exosome for degradation65,74. Mmi1 also directs RNAi-dependent heterochromatin formation and gene silencing through recruitment of Red1, the histone H3K9 methyltransferase Clr4/SUV39h, the RNA-induced transcriptional silencing (RITS) RNAi complex, and the conserved cleavage and polyadenylation factor (CPF)75,76,77,78. The role of Mmi1 in affecting chromatin accessibility and heterochromatin is similar to that of its human homolog YTHDC1.The presence of a YTH domain defines a group of proteins that includes YTHDF1-3, YTHDC1, and YTHDC2 in humans (Fig. 2A). After the YTH domain was first found to be able to bind single-stranded RNA, these five proteins were successively identified as m6A readers4,18,53,64,79. Through NMR spectroscopy and X-ray diffraction analysis, the solution and crystal structures of the YTH domains of distinct YTH family members and their complexes with m6A RNA oligoribonucleotides have been solved successively80,81. Overall, these YTH domains commonly adopt a specific mixed α-helix-β-sheet fold in which the β-sheets are arranged into a central, globular β-barrel fold and surrounded by α-helices, providing a hydrophobic core where several highly conserved aromatic residues are located. Electrostatic potential analysis of the protein surface demonstrated that the surface of the YTH domain has a positively charged concave structure, which is enriched with basic residues such as lysines and arginines and is responsible for RNA binding. Intriguingly, a well-defined conserved aromatic cage is observed in all YTH domains, which endows the YTH domain with the capacity for discriminative recognition of N6-methyladenosine-modified RNA (Fig. 2B).Fig. 2: The YTH domain is usually located in the C terminus of proteins and is rich in basic amino acid residues for RNA binding.A Schematic representation of the protein structure of human YTH domain-containing proteins (YTHDC1, YTHDC2, YTHDF1, YTHDF2, and YTHDF3). B, C The electrostatic potential surface of the YTH domains of YTHDC1 and YTHDF1 in complex with m6A-containing oligonucleotides is represented by PyMOL 2.0. Positive charges are colored blue, neutral charges are white, and negative charges are red.Full size imageThe first aromatic cage was discovered in the YTH domain of YTHDC1 and consists of two aromatic tryptophans (W377 and W428) and an atypical nonaromatic leucine (L439), which forms vital π-π interactions with the adenine base and hydrophobic interactions with the N6-methyl moiety79 (Fig. 3A). Mutation of either W377 or W428 abolishes the binding of YTHDC1 to m6A, highlighting its critical role in specifically recognizing N6-methylated adenine bases. In addition to the above fundamental hydrophobic interactions, the N atoms in the methyladenine base (N6, N3, and N1) form hydrogen bonds with three residues (S378, N363, and N367) of YTHDC1 adjacent to the cage, making the binding between YTHDC1 and m6A more stable (Fig. 3A). Interestingly, Xu et al. found that when N367 is mutated to D367, m6A binding of YTHDC1 is abolished. Considering the difference in the protonation state between N367 and D367, it is predicted that the N1 atom is in a deprotonated state and thus would preferentially bind to deprotonated N367 over protonated D36782. In addition, the detailed structural analysis further specified that the basic residues around the aromatic cage also make significant contributions to the binding affinity of YTHDC1 for m6A-modified RNA. For example, the cytidine in GG(m6A)CU not only forms one hydrogen bond with the side chain of R475 but is also stacked with the guanidinium group of R475 and the adjacent uracil through cation–π and π–π interactions, respectively. Mutating R475 to phenylalanine or an alanine reduces the binding affinity by 9-fold or over 100-fold, respectively, suggesting the importance of this residue in maintaining YTHDC1-RNA binding. Recently, the crystal structure of the YTHDC2 YTH domain was solved and compared with that of the YTHDC1 domain in complex with GG(m6A)CU oligonucleotides83. Similarly, the YTH domain of YTHDC2 contains three aromatic residues (W1310, W1360, and L1365) corresponding respectively to W377, W428, and L439 of YTHDC1, which constitute a conserved hydrophobic pocket for m6A recognition. Furthermore, a positively charged surface around the m6A binding pocket is also observed in the YTHDC2 YTH domain, indicating that YTHDC2 adopts an architecture similar to that of YTHDC1 to accommodate m6A RNA moieties.Fig. 3: The conserved aromatic residues and basic residues in the YTH domain are responsible for methylated adenosine (m6A) recognition and binding, respectively.A Superposition of the complex structures of the YTHDC1 YTH domain (YTH-YTHDC1)-m6A (pink), YTH-YTHDF1-m6A (green), YTH-YTHDF2-m6A (yellow), and YTH-YTHDF3-m6A (pale green), showing the conserved aromatic cage for specific recognition of the methyl group of m6A. Both the residues in the aromatic cage of YTHDC1 and the 6-methylated adenine base (m6A) are shown in the model as pink sticks, and the counterparts in YTHDF1, YTHDF2, and YTHDF3 are shown in the model as green, yellow, and pale green sticks, respectively. In addition, the adenine base always forms three hydrogen bonds with adjacent residues (cyan sticks), which is essential for the binding between m6A and YTH domains. The hydrogen bonds are labeled with dashed lines. The corresponding PDB IDs are 4R3I, 4RCJ, 4RDN, and 6ZOT. B Four basic residues, R411, K416, R441, and R527, on the surface of the YTHDF2 YTH domain, are critical for binding to the RNA backbone. C Superposition of the YTH domains of YTHDC1 (pink cartoon), YTHDC2 (cyan cartoon), YTHDF1 (green cartoon), YTHDF2 (yellow cartoon), and YTHDF3 (pale green cartoon). The four basic residues are highly conserved in these human YTH proteins. The basic residues R411, K416, R441, and R527 in YTHDF2 and their corresponding residues in the YTH domains of YTHDC1, YTHDC2, YTHDF1, and YTHDF3 are shown as yellow, pink, cyan, green, and pale green sticks.Full size imageWith the clarification of the YTHDC1–m6A complex structure, the structures of three cytoplasmic m6A readers, YTHDF1, YTHDF2, and YTHDF3, in complex with m6A-modified RNA have successively been solved by three individual groups40,82,84. Unsurprisingly, the YTH domains of YTHDF1, YTHDF2, and YTHDF3 harbor a specific m6A RNA-binding surface and aromatic cage similar to that of YTHDC1; this cage is composed of W411, W465, and W470 in YTHDF1; W432, W486, and W491 in YTHDF2; and W438, W492, and W497 in YTHDF3 (Fig. 3A). Mutating the above tryptophans to alanines drastically impairs the binding of YTHDF1 and YTHDF2 to m6A RNA. Additionally, three conserved residues in YTHDF1 (C412, Y397, and D401), YTHDF2 (C433, Y418, and D422), and YTHDF3 (C439, Y424, and D428) that are located near the aromatic cage and correspond to S378, N363, and N367 in YTHDC1 form hydrogen bonds with the N6 amino group in m6A, N3 in purine rings, and N1 in purine rings, respectively (Fig. 3A). Mutation of Y397 in YTHDF1 results in a marked decline in its m6A RNA binding, suggesting that these hydrogen bonds are also of great importance in m6A recognition. Of particular note is that N367 in YTHDC1 is substituted for D401 in YTHDF1, which may explain why the binding affinity of YTHDC1 for GG(m6A)CU (Kd = 2.0 μM) is ten times higher than that of YTHDF1 (Kd = 22.0 μM)82. Mutating D401 to N401 significantly enhances the binding capacity of YTHDF1, rendering it identical to that of YTHDC1 (Kd = 1.5 μM), confirming the considerable contribution of this specific residue to m6A RNA binding. Moreover, a basic patch composed of four basic residues, R411, K416, R441, and R527, is observed on the electrostatic potential surface of the YTHDF2 YTH domain85 (Fig. 3B). Sequence alignment of the five YTH domains showed that these four residues are almost completely conserved in YTHDF1-3 and YTHDC1-2 (Fig. 3C). The results of mutagenesis experiments demonstrated that mutating K416 and R527 of YTHDF2 to alanines not only heavily reduces the m6A binding affinity of YTHDF2 by approximately 25-fold but also decreases the binding of unmethylated RNA (A-RNA) by over 5-fold and 10-fold, respectively. Similarly, the binding affinity of the YTHDF2 R411A mutant for m6A RNA and A-RNA is decreased by ~3-fold and 2-fold, respectively, revealing that the basic patch on the surface of the YTH domain has a dominant role in binding to the RNA backbone but probably does not participate in m6A recognition. To more clearly delineate the molecular mechanisms underlying the specific recognition of m6A-modified RNA by human YTH family proteins, a summary of binding affinities of the wild-type and YTH domain mutants of YTHDC1, YTHDF1, and YTHDF2 to 5-mer and 17-mer m6A-modified RNA oligonucleotides are provided in Table 1.Table 1 Binding affinities of the wild-type and mutant YTH domains of YTHDC1, YTHDF1, and YTHDF2 for m6A-modified RNAs.Full size tableA previous study of the m6A RNA methylome by borate gel chromatography suggested that m6A modification is highly enriched in RRACU (where R is A or G) sequences in mammals86. Recent PAR-CLIP studies on transcriptome-wide YTHDC1 binding sites also identified GG(m6A)C as the highest affinity binding motif of YTHDC179. Furthermore, quantitative isothermal titration calorimetry (ITC) binding assay confirmed that the binding affinity of YTHDC1 for GG(m6A)CU (Kd = 2.0 μM) was severely impaired when the second G nucleotide (G-1) was replaced with A (A-1, Kd =15.0 μM). However, subsequent comprehensive analysis of the sequence preference of different YTH domains for m6A RNAs revealed that no YTH domain except for that in YTHDC1 exhibits sequence selectivity at the position preceding the m6A modification82 (Table 2). By superposition of the crystal structures of the YTHDF1-GG(m6A)CU and YTHDC1-GG(m6A)CU complexes, several key structural divergences were observed that may reasonably explain the unique nucleotide selectivity of YTHDC1 at the -1 position. First, G-1 (the G nucleotide preceding the m6A) forms two hydrogen bonds with V382 and N383 and interacts with L380 and M438 by hydrophobic interactions (Fig. 4), which might be abolished by replacing G-1 with A-1. Second, L380 and M438 are exclusive to YTHDC1, while their counterparts in other YTH proteins are polar amino acids, for example, T414 and K469 in YTHDF1 and T435 and K490 in YTHDF2. Mutating either of these two residues to an alanine not only impairs binding to m6A-containing 16-mer RNA oligonucleotides but also abolishes the sequence preference of YTHDC1 at the −1 position. In contrast, the G-1 nucleotide only forms one hydrophobic interaction with Y397 in YTHDF1, which may result in decreased selectivity between YTHDF1 and the G-1 nucleotide (Fig. 4). In summary, compared to other YTH domains, the YTHDC1 YTH domain adopts a unique G-1 binding pocket, by which YTHDC1 acquires selectivity for the nucleotide preceding the m6A.Table 2 Binding affinities of four human YTH family members (YTHDC1, YTHDC2, YTHDF1, and YTHDF2) to a 9-mer methylated RNA oligonucleotide.Full size tableFig. 4: Structural comparison of YTHDC1 and YTHDF1 reveals the structural basis for the discriminative recognition of the nucleotide preceding the m6A mark by YTHDC1.The YTHDC1-G(m6A) and YTHDF1-G(m6A) complexes are shown in the model as pink and green sticks, and the difference interactions between YTHDC1 and YTHDF1 with the G-1 nucleotide are highlighted with yellow dashed lines.Full size imageYTH family proteins’ roles in human cancerSince N6-methyladenosine modification affects gene expression during multiple steps of RNA metabolic processes, many studies have found that m6A is critical in many diseases, including cancer87,88. As important readers, YTH family proteins are involved in almost every aspect of tumorigenesis and cancer progression (Table 3).Table 3 List of the roles of YTH family proteins in different cancers.Full size tableYTHDF1’s role in human cancerAs mentioned above, YTHDF1, a reader of m6A, can promote the translation of some transcripts to change the proteome in cancer cells, therefore regulating tumorigenesis. Additionally, several kinds of tumors have been reported to be related to YTHDF1. Many studies have indicated that YTHDF1 is an oncogene. For example, YTHDF1 is highly expressed in intestinal stem cells and colorectal cancer cells, and it participates in Wnt signaling. YTHDF1 can facilitate the translation of Wnt signaling effectors, including TCF7L2/TCF4, to augment β-catenin activity to regulate intestinal stem cell activity and tumorigenesis89,90. Similarly, in gastric cancer, mutated YTHDF1 enhances the translation of FZD7 to activate the Wnt-β-catenin pathway to promote gastric cancer cell proliferation and tumorigenesis91. In non-small cell lung cancer (NSCLC), YTHDF1 was reported to promote cancer cell proliferation and tumor progression by regulating the translational efficiency of CDK2, CDK4, and cyclin D192. In addition, YTHDF1 helps promote YAP mRNA translation in NSCLC, and the increases in YAP expression and activity induce drug resistance and metastasis in NSCLC93. Abnormally controlled translation of key mRNAs in the cancer genome and generally enhanced translational output are important responses to oncogenic stimulation94. Indeed, in ovarian cancer, m6A-modified EIF3C, which is an essential initiation factor, is recognized and bound to YTHDF1. YTHDF1 promotes the translation of EIF3C and therefore enhances the total translational output, inducing cancer progression and metastasis95. It was also reported that YTHDF1 has an important role in bladder cancer. YTHDF1 helps promote the translation of ITGA6 and CDCP1 mRNA, and high expression of these factors can increase the growth and progression of bladder cancer96,97. Merkel cell carcinoma is deadly skin cancer in which YTHDF1 was found to be highly expressed and associated with tumorigenesis98. Additionally, YTHDF1 has been implicated in epithelial–mesenchymal transition (EMT), of which the transcription factor Snail is known to be a critical regulator. YTHDF1 was reported to mediate the m6A-increased translation of Snail mRNA and thus regulate EMT in cancer cells19. In the field of tumor immunotherapy, it was reported that durable neoantigen-specific immunity is suppressed by YTHDF1. Mechanistically, m6A-containing transcripts encoding lysosomal proteases are recognized by YTHDF1, and thus elevated expression at the translational level promotes the degradation of tumor neoantigens and represses cross-presentation to influence the efficacy of immunotherapy99. Moreover, there is some evidence indicating that YTHDF1 is associated with poor prognosis in patients with hepatocellular carcinoma and breast cancer100,101,102,103. However, YTHDF1 was also found to act as a tumor suppressor by promoting the translation of the methylated mRNA of HINT2, a tumor suppressor in ocular melanoma104.YTHDF2’s role in human cancerAnother important reader, YTHDF2, is also well researched and has been found to be closely related to human cancer. Among the many different kinds of tumors, hepatocellular carcinoma (HCC) is one in which YTHDF2 has been studied the most. YTHDF2 can influence tumor progression in several different ways. YTHDF2 generally works as a tumor suppressor in HCC, as it mediates the decay of m6A-containing IL11 and SERPINE2 mRNAs, which are mediators of cancer-promoting inflammation and reprogramming of the tumor vasculature69. YTHDF2 also suppresses ERK/MAPK signaling by destabilizing EGFR in an m6A-dependent manner to inhibit the growth and proliferation of HCC cells105. Moreover, YTHDF2 participates in HCC progression in another way, although it does not have a core role. It binds SOCS2 mRNA and mediates its degradation to promote liver cancer progression, while METTL3 regulates the m6A level of SOCS2 mRNA106. It was reported that miR-145 targets the 3′ UTR of YTHDF2 mRNA, thus affecting the decay of m6A-containing mRNA to influence the m6A level in HCC cells. However, this research showed that YTHDF2 was closely associated with the malignancy of HCC107. Indeed, another research group regarded YTHDF2 as an oncogene in HCC because they found that YTHDF2 increased OCT4 expression to promote liver cancer metastasis108,109. Regarding other types of cancer, YTHDF2 is overexpressed in acute myeloid leukemia and is required for disease initiation. Mechanistically, YTHDF2 destabilizes m6A-modified transcripts such as that of the tumor necrosis factor receptor Tnfrsf2 to protect self-renewing leukemic stem cells against apoptosis110. YTHDF2 promotes the proliferation and inhibits the migration and invasion as well as EMT of pancreatic cancer cells, probably through YAP signaling, although the exact mechanism remains to be clarified111. The oncogenicity of YTHDF2 was revealed in prostate cancer, and YTHDF2 mediates the degradation of LHPP and NKX3-1 to induce the phosphorylation of AKT112. In glioblastoma, in contrast to its proposed role, YTHDF2 was shown to stabilize MYC and VEGFA to maintain the oncogenic phenotype of glioblastoma stem cells113. It was also reported that YTHDF2 was phosphorylated at serine 39 and threonine 381 through EGFR/SRC/ERK signaling in glioblastoma114. The phosphorylation of YTHDF2 stabilized the YTHDF2 protein and promoted the decay of LXRA and HIVEP2 mRNA, which is required for cholesterol dysregulation, cell proliferation, invasion, and tumorigenesis in glioblastoma. Interestingly, although YTHDF2 was regarded to control mRNA decay, YTHDF2 was reported to facilitate 6PGD mRNA translation to promote lung cancer cell growth115, similar to the role of YTHDF1 and the same effect as the increased OCT4 expression mentioned above108. Notably, YTHDF2 has an important role in the regulatory effects of m6A methylases and demethylases on the tumorigenicity of osteosarcoma, breast tumors, melanoma, bladder cancer, pancreatic cancer, and colorectal cancer116,117,118,119,120,121,122,123.Other readers in human cancerThe other three YTH family proteins, YTHDF3, YTHDC1, and YTHDC2, were found to be less correlated with human cancer than YTHDF1 and YTHDF2. Recently, YTHDF3 was found to be overexpressed and enhance the translation of ST6GALNAC5, GJA1, and EGFR to promote brain metastasis in breast cancer109. A negative functional loop constituted by the lncRNA GAS5-YAP-YTHDF3 axis was revealed in colorectal cancer, as GAS5 interacts with the WW domain of YAP to facilitate YAP shuttling from the nucleus to the cytoplasm and YAP phosphorylation; subsequently, YAP is degraded in a ubiquitin-mediated manner to inhibit CRC progression. Importantly, YTHDF3 is a target of YAP signaling and mediates the decay of m6A-modified GAS5 mRNA124. Regarding YTHDF3, research in NSCLC revealed the mechanism by which YTHDF3 acts as a hub to fine-tune the accessibility of RNA to YTHDF1 and YTHDF230. As demonstrated above, YAP mRNA is recognized by YTHDF3 and is then assigned to YTHDF1 or YTHDF2 to be destabilized or translated; therefore, YTHDF3 is able to control YAP signaling to regulate cell proliferation, metastasis, and other tumorigenic behaviors. In addition, YTHDC1, which is an m6A reader involved in RNA splicing, was reported to recognize m6A modification around the start codon of serine/arginine-rich splicing factors (SRSFs) and lead to nonsense-mediated mRNA decay, which affects the alternative splicing of a number of genes, such as BCL-X and NCOR2, eventually causing cancer-related phenotypes mediated by METTL3 in glioblastoma125. In addition, the ability of YTHDC1 to splice transcripts has been demonstrated for a vascular endothelial growth factor (VEGF), breast cancer 1 (BRCA1), and the progesterone receptor (PGR) in endometrial carcinoma, but whether these processes are dependent on m6A modification is still unclear126,127. YTHDC2, the last reader, was reported to be upregulated in human cancer cell lines and to promote cancer metastasis by promoting translation initiation via unwinding of the 5′-untranslated region (5′ UTR) of mRNAs such as HIF-1α128. Moreover, YTHDC2 was found to be highly expressed in radioresistant nasopharyngeal carcinoma and to promote radioresistance by activating the IGF1R/ATK/S6 signaling axis129. YTHDC2 also regulates redox homeostasis and inhibits LUAD tumorigenesis since it promotes m6A-dependent mRNA degradation of SLC7A11, which is the core component of a cystine/glutamate antiporter130.Conclusions and perspectivesIn the early years, studies about the association between m6A modification and human cancer were centered around the balance of m6A addition and removal by writers and erasers, respectively6,131,132,133. However, changes in the readers could be a more crucial factor in the fate of RNAs. Therefore, we ask whether the switch from one reader to another could be a more reasonable strategy to control gene expression. Indeed, readers have recently been increasingly emphasized in epigenetic m6A modifications. Since domains other than the YTH domain of YTHDFs may only function after the binding process, it is likely that the YTH domain is responsible for recognizing target mRNAs. However, the targets of different readers have a certain degree of overlap, and the mechanism underlying the selectivity of readers is not well understood and may involve preferred motifs, phase separation, or the possible assigning function of YTHDF3 and other unknown factors. The upstream regulation of YTH family proteins is still unclear, although it has been found that miR-145 may affect YTHDF2 mRNA107. It is worth noting that there is an emerging concept that YTHDF proteins are redundant in function and that their only effect is destabilizing transcripts, which makes this field more complicated. In different types of tumor cells, the specific regulatory mechanism of m6A differs. It is possible that the functions of different readers can partially overlap, and this possibility still needs to be further investigated. From the perspectives of translational medicine and clinical medicine, drugs targeting the YTH family may be a potential strategy for certain cancers. Although specific chemical inhibitors targeting the YTH domain have yet to be discovered, the above investigation of the structural biology of different YTH domains has paved the way for the rational design of small-molecule YTH domain inhibitors. Notably, through a recent virtual screen and crystallographic analysis, Rajiv et al. identified some promising hits as competitive YTH domain modulators that were expected to efficiently disrupt the interactions between m6A and YTHDC1. Specifically, the author indicated that N-methyl amides could constitute appropriate fragments to compete with m6A molecules. Overall, considering the importance of the YTH family in cancer progression, the development of specific YTH domain inhibitors would not only enhance our knowledge of cancer epigenetics but also provide novel targeted therapies.

ReferencesDesrosiers, R., Friderici, K. & Rottman, F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl Acad. Sci. USA 71, 3971–3975 (1974).Article

CAS

PubMed

PubMed Central

Google Scholar

Csepany, T., Lin, A., Baldick, C. J. Jr & Beemon, K. Sequence specificity of mRNA N6-adenosine methyltransferase. J. Biol. Chem. 265, 20117–20122 (1990).Article

CAS

PubMed

Google Scholar

Meyer, K. D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell 149, 1635–1646 (2012).Article

CAS

PubMed

PubMed Central

Google Scholar

Dominissini, D. et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201–206 (2012).Article

CAS

PubMed

Google Scholar

Zhou, K. I. & Pan, T. An additional class of m(6)A readers. Nat. Cell Biol. 20, 230–232 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Chen, X. Y., Zhang, J. & Zhu, J. S. The role of m(6)A RNA methylation in human cancer. Mol. Cancer 18, 103 (2019).Article

PubMed

PubMed Central

Google Scholar

Peritz, T. et al. Immunoprecipitation of mRNA-protein complexes. Nat. Protoc. 1, 577–580 (2006).Article

CAS

PubMed

Google Scholar

Ule, J. et al. CLIP identifies Nova-regulated RNA networks in the brain. Science 302, 1212–1215 (2003).Article

CAS

PubMed

Google Scholar

Hafner, M. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129–141 (2010).Article

CAS

PubMed

PubMed Central

Google Scholar

Wang, X. et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505, 117–120 (2014).Article

CAS

PubMed

Google Scholar

Liu, J. et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93–95 (2014).Article

CAS

PubMed

Google Scholar

Ping, X. L. et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24, 177–189 (2014).Article

CAS

PubMed

PubMed Central

Google Scholar

Patil, D. P. et al. m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537, 369–373 (2016).Article

CAS

PubMed

PubMed Central

Google Scholar

Yue, Y. et al. VIRMA mediates preferential m(6)A mRNA methylation in 3’UTR and near stop codon and associates with alternative polyadenylation. Cell Discov. 4, 10 (2018).Article

PubMed

PubMed Central

CAS

Google Scholar

Wen, J. et al. Zc3h13 regulates nuclear RNA m(6)A methylation and mouse embryonic stem cell self-renewal. Mol. Cell 69, 1028–1038 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Jia, G. et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885–887 (2011).Article

CAS

PubMed

PubMed Central

Google Scholar

Zheng, G. et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49, 18–29 (2013).Article

CAS

PubMed

Google Scholar

Wang, X. et al. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388–1399 (2015).Article

CAS

PubMed

PubMed Central

Google Scholar

Lin, X. et al. RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail. Nat. Commun. 10, 2065 (2019).Article

PubMed

PubMed Central

CAS

Google Scholar

Zhao, W. et al. METTL3 facilitates oral squamous cell carcinoma tumorigenesis by enhancing c-Myc stability via YTHDF1-mediated m(6)A modification. Mol. Ther. Nucleic Acids 20, 1–12 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Lin, Z. et al. RNA m(6) A methylation regulates sorafenib resistance in liver cancer through FOXO3-mediated autophagy. EMBO J. 39, e103181 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Wang, Q. et al. N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification. Cell Death Dis. 11, 911 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Weng, Y. L. et al. Epitranscriptomic m(6)A regulation of axon regeneration in the adult mammalian nervous system. Neuron 97, 313–325 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Zhuang, M. R. et al. The m(6)A reader YTHDF1 regulates axon guidance through translational control of Robo3.1 expression. Nucleic Acids Res. 47, 4765–4777 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Shi, H. L. et al. m(6)A facilitates hippocampus-dependent learning and memory through YTHDF1. Nature 563, 249 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Du, H. et al. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat. Commun. 7, 12626 (2016).Article

CAS

PubMed

PubMed Central

Google Scholar

Zhao, B. S. et al. m(6)A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature 542, 475–478 (2017).Article

CAS

PubMed

PubMed Central

Google Scholar

Park, O. H. et al. Endoribonucleolytic cleavage of m(6)A-containing RNAs by RNase P/MRP complex. Mol. Cell 74, 494–507.e8 (2019).Shi, H. et al. YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified RNA. Cell Res. 27, 315–328 (2017).Article

CAS

PubMed

PubMed Central

Google Scholar

Jin, D. et al. m(6)A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Mol. Cancer 19, 40 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Ries, R. J. et al. m(6)A enhances the phase separation potential of mRNA. Nature 571, 424–428 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Gao, Y. et al. Multivalent m(6)A motifs promote phase separation of YTHDF proteins. Cell Res. 29, 767–769 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Wang, J. et al. Binding to m(6)A RNA promotes YTHDF2-mediated phase separation. Protein Cell 11, 304–307 (2020).Article

PubMed

Google Scholar

Fu, Y. & Zhuang, X. m(6)A-binding YTHDF proteins promote stress granule formation. Nat. Chem. Biol. 16, 955–963 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Zhou, J. et al. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature 526, 591–594 (2015).Article

CAS

PubMed

PubMed Central

Google Scholar

Panneerdoss, S. et al. Cross-talk among writers, readers, and erasers of m(6)A regulates cancer growth and progression. Sci. Adv. 4, eaar8263 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Song, T. et al. Zfp217 mediates m6A mRNA methylation to orchestrate transcriptional and post-transcriptional regulation to promote adipogenic differentiation. Nucleic Acids Res. 47, 6130–6144 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Zaccara, S. & Jaffrey, S. R. A unified model for the function of YTHDF proteins in regulating m(6)A-modified mRNA. Cell 181, 1582–1595 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Lasman, L. et al. Context-dependent functional compensation between Ythdf m(6)A reader proteins. Genes Dev. 34, 1373–1391 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Li, Y., Bedi, R. K., Moroz-Omori, E. V. & Caflisch, A. Structural and dynamic insights into redundant function of YTHDF proteins. J. Chem. Inf. Model 60, 5932–5935 (2020).Article

CAS

PubMed

Google Scholar

Imai, Y., Matsuo, N., Ogawa, S., Tohyama, M. & Takagi, T. Cloning of a gene, YT521, for a novel RNA splicing-related protein induced by hypoxia/reoxygenation. Brain Res. Mol. Brain Res. 53, 33–40 (1998).Article

CAS

PubMed

Google Scholar

Nayler, O., Hartmann, A. M. & Stamm, S. The ER repeat protein YT521-B localizes to a novel subnuclear compartment. J. Cell Biol. 150, 949–962 (2000).Article

CAS

PubMed

PubMed Central

Google Scholar

Hartmann, A. M., Nayler, O., Schwaiger, F. W., Obermeier, A. & Stamm, S. The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn). Mol. Biol. Cell 10, 3909–3926 (1999).Article

CAS

PubMed

PubMed Central

Google Scholar

Rafalska, I. et al. The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation. Hum. Mol. Genet. 13, 1535–1549 (2004).Article

CAS

PubMed

Google Scholar

Xiao, W. et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol. Cell 61, 507–519 (2016).Article

CAS

PubMed

Google Scholar

Roundtree, I. A. et al. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife 6, e31311 (2017).Haussmann, I. U. et al. m(6)A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 540, 301–304 (2016).Article

CAS

PubMed

Google Scholar

Lence, T. et al. m(6)A modulates neuronal functions and sex determination in Drosophila. Nature 540, 242–247 (2016).Article

CAS

PubMed

Google Scholar

Liu, J. et al. N (6)-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367, 580–586 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Shima, H. et al. S-adenosylmethionine synthesis is regulated by selective N(6)-adenosine methylation and mRNA degradation Involving METTL16 and YTHDC1. Cell Rep. 21, 3354–3363 (2017).Article

CAS

PubMed

Google Scholar

Li, Y. et al. N(6)-methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2. Nat. Genet. 52, 870–877 (2020).Article

CAS

PubMed

Google Scholar

Morohashi, K. et al. Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B. PLoS ONE 6, e18285 (2011).Article

CAS

PubMed

PubMed Central

Google Scholar

Hsu, P. J. et al. Ythdc2 is an N(6)-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Res. 27, 1115–1127 (2017).Article

CAS

PubMed

PubMed Central

Google Scholar

Wojtas, M. N. et al. Regulation of m(6)A transcripts by the 3’->5’ RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline. Mol. Cell 68, 374–387 (2017).Article

CAS

PubMed

Google Scholar

Abby, E. et al. Implementation of meiosis prophase I programme requires a conserved retinoid-independent stabilizer of meiotic transcripts. Nat. Commun. 7, 10324 (2016).Article

CAS

PubMed

PubMed Central

Google Scholar

Soh, Y. Q. S. et al. Meioc maintains an extended meiotic prophase I in mice. PLoS Genet. 13, e1006704 (2017).Article

PubMed

PubMed Central

CAS

Google Scholar

Bailey, A. S. et al. The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline. Elife 6, e26116 (2017).Jain, D. et al. ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2. Elife 7, e30919 (2018).Kretschmer, J. et al. The m(6)A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5’-3’ exoribonuclease XRN1. RNA 24, 1339–1350 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Mao, Y. et al. m(6)A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2. Nat. Commun. 10, 5332 (2019).Article

PubMed

PubMed Central

Google Scholar

Nakano, M., Ondo, K., Takemoto, S., Fukami, T. & Nakajima, M. Methylation of adenosine at the N(6) position post-transcriptionally regulates hepatic P450s expression. Biochem Pharm. 171, 113697 (2020).Article

CAS

PubMed

Google Scholar

Zhou, B. et al. N(6) -Methyladenosine Reader Protein YT521-B Homology Domain-Containing 2 Suppresses Liver Steatosis by Regulation of mRNA Stability of Lipogenic Genes. Hepatology 73, 91–103 (2021).Article

CAS

PubMed

Google Scholar

Stoilov, P., Rafalska, I. & Stamm, S. YTH: a new domain in nuclear proteins. Trends Biochem. Sci. 27, 495–497 (2002).Article

CAS

PubMed

Google Scholar

Zhang, Z. et al. The YTH domain is a novel RNA binding domain. J. Biol. Chem. 285, 14701–14710 (2010).Article

CAS

PubMed

PubMed Central

Google Scholar

Harigaya, Y. et al. Selective elimination of messenger RNA prevents an incidence of untimely meiosis. Nature 442, 45–50 (2006).Article

CAS

PubMed

Google Scholar

Kang, H. J. et al. A novel protein, Pho92, has a conserved YTH domain and regulates phosphate metabolism by decreasing the mRNA stability of PHO4 in Saccharomyces cerevisiae. Biochem. J. 457, 391–400 (2014).Article

CAS

PubMed

Google Scholar

Baumgarten, S. et al. Transcriptome-wide dynamics of extensive m(6)A mRNA methylation during Plasmodium falciparum blood-stage development. Nat. Microbiol. 4, 2246–2259 (2019).Article

PubMed

CAS

PubMed Central

Google Scholar

Li, D. Y. et al. Genome-wide identification, biochemical characterization, and expression analyses of the YTH domain-containing RNA-binding protein family in Arabidopsis and rice. Plant Mol. Biol. Rep. 32, 1169–1186 (2014).Article

CAS

Google Scholar

Wang, N., Yue, Z., Liang, D. & Ma, F. Genome-wide identification of members in the YTH domain-containing RNA-binding protein family in apple and expression analysis of their responsiveness to senescence and abiotic stresses. Gene 538, 292–305 (2014).Article

CAS

PubMed

Google Scholar

Sun, J., Bie, X. M., Wang, N., Zhang, X. S. & Gao, X. Q. Genome-wide identification and expression analysis of YTH domain-containing RNA-binding protein family in common wheat. BMC Plant Biol. 20, 351 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Govindaraju, G. et al. 6-Adenosine methylation on mRNA is recognized by YTH2 domain protein of human malaria parasite Plasmodium falciparum. Epigenet. Chromatin 13, 33 (2020).Arribas-Hernandez, L. et al. An m(6)A-YTH module controls developmental timing and morphogenesis in Arabidopsis. Plant Cell 30, 952–967 (2018).Article

CAS

PubMed

PubMed Central

Google Scholar

Arribas-Hernandez, L. et al. Recurrent requirement for the m(6)A-ECT2/ECT3/ECT4 axis in the control of cell proliferation during plant organogenesis. Development 147, dev189134 (2020).Yamashita, A. et al. Hexanucleotide motifs mediate recruitment of the RNA elimination machinery to silent meiotic genes. Open Biol. 2, 120014 (2012).Article

PubMed

PubMed Central

CAS

Google Scholar

Zofall, M. et al. RNA elimination machinery targeting meiotic mRNAs promotes facultative heterochromatin formation. Science 335, 96–100 (2012).Article

CAS

PubMed

Google Scholar

Tashiro, S., Asano, T., Kanoh, J. & Ishikawa, F. Transcription-induced chromatin association of RNA surveillance factors mediates facultative heterochromatin formation in fission yeast. Genes Cells 18, 327–339 (2013).Article

CAS

PubMed

Google Scholar

Hiriart, E. et al. Mmi1 RNA surveillance machinery directs RNAi complex RITS to specific meiotic genes in fission yeast. EMBO J. 31, 2296–2308 (2012).Article

CAS

PubMed

PubMed Central

Google Scholar

Vo, T. V. et al. CPF recruitment to non-canonical transcription termination sites triggers heterochromatin assembly and gene silencing. Cell Rep. 28, 267–281 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Xu, C. et al. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat. Chem. Biol. 10, 927–929 (2014).Article

CAS

PubMed

Google Scholar

Theler, D., Dominguez, C., Blatter, M., Boudet, J. & Allain, F. H. Solution structure of the YTH domain in complex with N6-methyladenosine RNA: a reader of methylated RNA. Nucleic Acids Res. 42, 13911–13919 (2014).Article

CAS

PubMed

PubMed Central

Google Scholar

Luo, S. & Tong, L. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proc. Natl Acad. Sci. USA 111, 13834–13839 (2014).Article

CAS

PubMed

PubMed Central

Google Scholar

Xu, C. et al. Structural basis for the discriminative recognition of N6-methyladenosine RNA by the human YT521-B homology domain family of proteins. J. Biol. Chem. 290, 24902–24913 (2015).Article

CAS

PubMed

Google Scholar

Ma, C., Liao, S. & Zhu, Z. Crystal structure of human YTHDC2 YTH domain. Biochem. Biophys. Res. Commun. 518, 678–684 (2019).Article

CAS

PubMed

Google Scholar

Li, F., Zhao, D., Wu, J. & Shi, Y. Structure of the YTH domain of human YTHDF2 in complex with an m(6)A mononucleotide reveals an aromatic cage for m(6)A recognition. Cell Res. 24, 1490–1492 (2014).Article

PubMed

PubMed Central

CAS

Google Scholar

Zhu, T. et al. Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell Res. 24, 1493–1496 (2014).Article

CAS

PubMed

PubMed Central

Google Scholar

Wei, C. M. & Moss, B. Nucleotide sequences at the N6-methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry 16, 1672–1676 (1977).Article

CAS

PubMed

Google Scholar

He, L. et al. Functions of N6-methyladenosine and its role in cancer. Mol. Cancer 18, 176 (2019).Article

PubMed

PubMed Central

Google Scholar

Huang, H., Weng, H. & Chen, J. m(6)A modification in coding and non-coding RNAs: roles and therapeutic implications in cancer. Cancer Cell 37, 270–288 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Bai, Y. et al. YTHDF1 regulates tumorigenicity and cancer stem cell-like activity in human colorectal carcinoma. Front. Oncol. 9, 332 (2019).Article

PubMed

PubMed Central

Google Scholar

Han, B. et al. YTHDF1-mediated translation amplifies Wnt-driven intestinal stemness. EMBO Rep. 21, e49229 (2020).Pi, J. et al. YTHDF1 promotes gastric carcinogenesis by controlling translation of FZD7. Cancer Res. (2020).Shi, Y. et al. YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat. Commun. 10, 4892 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Jin, D. et al. m(6)A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis. J. Hematol. Oncol. 12, 135 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Truitt, M. L. & Ruggero, D. New frontiers in translational control of the cancer genome. Nat. Rev. Cancer 16, 288–304 (2016).Article

CAS

PubMed

PubMed Central

Google Scholar

Liu, T. et al. The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation. Nucleic Acids Res. 48, 3816–3831 (2020).Jin, H. et al. N(6)-methyladenosine modification of ITGA6 mRNA promotes the development and progression of bladder cancer. EBioMedicine 47, 195–207 (2019).Article

PubMed

PubMed Central

Google Scholar

Yang, F. et al. Dynamic m(6)A mRNA methylation reveals the role of METTL3-m(6)A-CDCP1 signaling axis in chemical carcinogenesis. Oncogene 38, 4755–4772 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Orouji, E., Peitsch, W. K., Orouji, A., Houben, R. & Utikal, J. Oncogenic role of an epigenetic reader of m(6)A RNA modification: YTHDF1 in merkel cell carcinoma. Cancers 12, 202 (2020).Han, D. L. et al. Anti-tumour immunity controlled through mRNA m(6)A methylation and YTHDF1 in dendritic cells. Nature 566, 270 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Zhao, X. G. et al. Overexpression of YTHDF1 is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Biomark. 21, 859–868 (2018).Article

CAS

PubMed

Google Scholar

Zhou, Y. et al. Expression profiles and prognostic significance of RNA N6-methyladenosine-related genes in patients with hepatocellular carcinoma: evidence from independent datasets. Cancer Manag. Res. 11, 3921–3931 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Liu, L. et al. N6-methyladenosine-related genomic targets are altered in breast cancer tissue and associated with poor survival. J. Cancer 10, 5447–5459 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Qu, N. et al. Multiple m(6)A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis. BMC Cancer 20, 165 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Jia, R. et al. m(6)A modification suppresses ocular melanoma through modulating HINT2 mRNA translation. Mol. Cancer 18, 161 (2019).Article

PubMed

PubMed Central

CAS

Google Scholar

Zhong, L. et al. YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer Lett. 442, 252–261 (2019).Article

CAS

PubMed

Google Scholar

Chen, M. et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology 67, 2254–2270 (2018).Article

CAS

PubMed

Google Scholar

Yang, Z. et al. MicroRNA-145 modulates N(6)-methyladenosine levels by targeting the 3’-untranslated mRNA region of the N(6)-methyladenosine binding YTH domain family 2 protein. J. Biol. Chem. 292, 3614–3623 (2017).Article

CAS

PubMed

PubMed Central

Google Scholar

Zhang, C. et al. YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation. Oncogene 39, 4507–4518 (2020).Article

CAS

PubMed

Google Scholar

Chang, G. et al. YTHDF3 induces the translation of m(6)A-enriched gene transcripts to promote breast cancer brain metastasis. Cancer Cell 38, 857–871 e857 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Paris, J. et al. Targeting the RNA m(6)A reader YTHDF2 selectively compromises cancer stem cells in acute myeloid leukemia. Cell Stem Cell 25, 137–148 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Chen, J. et al. YTH domain family 2 orchestrates epithelial-mesenchymal transition/proliferation dichotomy in pancreatic cancer cells. Cell Cycle 16, 2259–2271 (2017).Article

CAS

PubMed

PubMed Central

Google Scholar

Li, J. et al. YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer. Mol. Cancer 19, 152 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Dixit, D. et al. The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells. Cancer Discov 11, 480–499 (2020).Article

PubMed

PubMed Central

Google Scholar

Fang, R. et al. EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma. Nat. Commun. 12, 177 (2021).Article

CAS

PubMed

PubMed Central

Google Scholar

Sheng, E. et al. YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation. Carcinogenesis 41, 541–550 (2019).Article

CAS

Google Scholar

Chen, S., Zhou, L. & Wang, Y. ALKBH5-mediated m(6)A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma. Cancer Cell Int 20, 34 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Niu, Y. et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3. Mol. Cancer 18, 46 (2019).Article

PubMed

PubMed Central

Google Scholar

Yang, S. et al. m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat. Commun. 10, 2782 (2019).Article

PubMed

PubMed Central

CAS

Google Scholar

Xie, H. et al. METTL3/YTHDF2 m(6) A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer. J. Cell Mol. Med. 24, 4092–4104 (2020).Yang, X. et al. METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Mol. Cancer 19, 46 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Tian, J. et al. N(6)-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Gut 69, 2180–2192 (2020).Chen, X. et al. METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Mol. Cancer 19, 106 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Guo, X. et al. RNA demethylase ALKBH5 prevents pancreatic cancer progression by posttranscriptional activation of PER1 in an m6A-YTHDF2-dependent manner. Mol. Cancer 19, 91 (2020).Article

CAS

PubMed

PubMed Central

Google Scholar

Ni, W. et al. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m(6)A reader YTHDF3. Mol. Cancer 18, 143 (2019).Article

PubMed

PubMed Central

Google Scholar

Li, F. et al. N(6)-methyladenosine modulates nonsense-mediated mRNA decay in human glioblastoma. Cancer Res. 79, 5785–5798 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Zhang, B. et al. YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A. Tumour Biol. 37, 15543–15549 (2015).Hirschfeld, M. et al. Hypoxia-dependent mRNA expression pattern of splicing factor YT521 and its impact on oncological important target gene expression. Mol. Carcinog. 53, 883–892 (2014).Article

CAS

PubMed

Google Scholar

Tanabe, A. et al. RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1alpha mRNA is translated. Cancer Lett. 376, 34–42 (2016).Article

CAS

PubMed

Google Scholar

He, J. J. et al. m(6)A reader YTHDC2 promotes radiotherapy resistance of nasopharyngeal carcinoma via activating IGF1R/AKT/S6 signaling axis. Front. Oncol. 10, 1166 (2020).Article

PubMed

PubMed Central

Google Scholar

Ma, L. et al. The m(6)A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function. Redox Biol. 38, 101801 (2021).Article

CAS

PubMed

Google Scholar

Weng, H. et al. METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification. Cell Stem Cell 22, 191–205 (2018).Article

CAS

PubMed

Google Scholar

Huang, Y. et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell 35, 677–691 (2019).Article

CAS

PubMed

PubMed Central

Google Scholar

Cheng, M. et al. The m(6)A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-kappaB/MYC signaling network. Oncogene 38, 3667–3680 (2019).Article

CAS

PubMed

Google Scholar

Download referencesAcknowledgementsWe thank members of our laboratories for their suggestions and help.FundingThe authors received no specific funding for this work.Author informationAuthor notesThese authors contributed equally: Rongkai Shi, Shilong YingAuthors and AffiliationsLaboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Cancer Center, Zhejiang University, Hangzhou, ChinaRongkai Shi, Shilong Ying, Yadan Li, Liyuan Zhu & Hongchuan JinDepartment of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, ChinaXian WangAuthorsRongkai ShiView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsH.J., X.W., and R.S. designed the study. R.S. and S.Y. collected the related references, wrote the manuscript, and constructed the figures. H.J., R.S., S.Y., Y.L., and L.Z. revised the manuscript. All authors approved the final manuscript and agreed to be responsible for this review.Corresponding authorCorrespondence to

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Reprints and permissionsAbout this articleCite this articleShi, R., Ying, S., Li, Y. et al. Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics.

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YTH N6-甲基腺苷 RNA 结合蛋白 2（YTHDF2）基因 | MCE

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NCB: 一种新的m6A阅读器！可促进mRNA翻译和稳定性 - 知乎

NCB: 一种新的m6A阅读器！可促进mRNA翻译和稳定性 - 知乎切换模式写文章登录/注册NCB: 一种新的m6A阅读器！可促进mRNA翻译和稳定性表观生物Welcome to epigenetics landscape.m6A是在真核细胞mRNA中最普遍存在的修饰，需由阅读器 (reader) 识别 (比如YTH结构域蛋白)，调控mRNA的命运。近日，中山大学杨建华教授团队、辛辛那提大学陈建军教授以及芝加哥大学何川教授团队等合作，发现IGF2BP蛋白 (胰岛素样生长因子2 mRNA 结合蛋白) 是一种独特的m6A阅读器，它不像YTH结构域家族蛋白那样促进mRNA降解，而是使mRNA更稳定！咱们来看看他们是如何发现这种新reader的：发现IGF2BP是m6A结合蛋白研究者通过两个方法，筛选m6A结合蛋白：1. 使用甲基化的单链RNA诱饵 (ss-m6A，共有序列为GG(m6A)CU)，对照组为未甲基化的RNA (ss-A)，进行RNA pull-down和质谱分析；2. 利用自主研发的一个新计算流程：基于已发表的RBP CLIP-seq (紫外交联免疫共沉淀测序) 数据库和已知的m6A修饰位点，筛选出潜在m6A结合蛋白。a.质谱分析表明3种IGF2BP蛋白与ss-m6A结合。b.计算结果表明这3种IGF2BP在112个显著的RBP里面排前15。c. FLAG-IGF2BP上富集有m6A修饰。d. 对比RIP-seq结果和已发表的PAR-CLIP数据，找到3种IGF2BP蛋白的高可信度靶基因。通过这种方法，研究者鉴定得IGF2BP为m6A结合蛋白。发现IGF2BP能使靶基因更稳定为探究IGF2BP的作用，研究者进行了功能缺失实验，即敲降IGF2BP，进行RNA-seq，发现靶基因的表达因此减少：CLIP组靶基因 (CLIP数据所示的靶基因) 表达被抑制，特别是CLIP+RIP组靶基因 (RIP-seq与CLIP数据重叠的靶基因)。IGF2BP的这个功能否受胞内m6A水平影响呢？降低m6A水平，常用的方法是敲降甲基转移酶METTL3或METTL14 ；研究者敲降HepG2细胞的METTL14后，进行m6A-seq和RNA-seq，发现有1,516个基因的m6A修饰相应减少，其中有418个基因的mRNA水平下降，而IGF2BP的高可信靶基因都在此列，下调显著。IGF2BP和METTL14的关联表明IGF2BP与m6A调控的基因相关。d. HepG2细胞敲降METTL14后的m6A水平与基因表达水平，两者均下降的418个基因即为m6A-Hypo-down组；e. shMETTL14细胞中IGF2BP高可信靶基因的mRNA log2 FC累积频数；f. METTL3或METTL14沉默后FSCN1、TK1、MARCKSL1 和MYC mRNA水平。研究者敲降了细胞的IGF2BP3，检测mRNA稳定性，发现IGF2BP3和CLIP的高可信度靶基因的中位半衰期都显著缩短了将近一半！还有哪些因子共同增强mRNA的稳定性呢？研究者对IGF2BP2复合物进行了pull down与质谱分析，发现存在着ELAVL1 (也叫HuR)，MATR3和PABPC1，这3个都是已知的mRNA稳定剂（mRNA stabilizers）。以上结果表明IGF2BP2有助于其靶基因稳定翻译。发现m6A对IGF2BP的作用MYC是IGF2BP1的靶基因，研究者发现m6A修饰在MYC上积累，且m6A的峰与IFG2BP结合位点一致；CRD区 (不稳定编码区) 的m6A修饰丰度很高，且在METTL14敲降后显著减少；通过RIP和基因特异m6A实验，研究者证明CRD区域内存在IGF2BP结合、m6A修饰、METTL3和METTL13的结合：a, m6A-seq和RIP-seq所得的MYC mRNA与m6A峰的分布图；b, RIP–qPCR显示MYC CRD中的FLAG-tagged IGF2BPs；c, gene-specific m6A qPCR实验检测MYC CRD的m6A修饰；d, RIP–qPCR 显示METTL3和METTL14 结合到m6A CRD. e, RNA pull down，分别用有m6A或者没有m6A修饰的CRD1、CRD2来拉IGF2BP。接下来，研究者利用荧光素酶报告实验，检测突变CRD序列之后IGF2BP的表达情况；联合RIP-qPCR实验，证明CRD的m6A修饰对IGF2BP结合到MYC以及调节MYC表达是必需的。研究者还发现KH3-4双结构域对IGF2BP与带m6A修饰的mRNA的结合，以及调控靶基因有着重要的作用。验证IGF2BP的致癌作用Cancer Genomics cBioPortal与TCGA的数据显示，3种IGF2BP在多种肿瘤中均有异常高表达，联系本研究中它们对致癌基因如MYC的稳定作用，研究者推测IGF2BP具有致癌作用，于是他敲降了HeLa和HepG2细胞的IGF2BP，结果抑制了这些肿瘤细胞的增殖、克隆形成能力和细胞迁移/侵袭，效果如同沉默MYC；利用CRISPR-Cas9技术敲除IGF2BP，再添加KH3-4突变的IGF2BP进行挽救实验，证明IGG2BP的致癌功能依赖于KH3-4，即m6A reader。 Epi老师：值得一提的是，NCB杂志同期还配发了题为“An additional class of m6A readers”的评述文章，对该工作给予了高度评价。这项研究鉴定得新的m6A识别蛋白家族IGF2BP1/2/3，并且发现它有着与已知的YTH结构域蛋白有着截然不同的功能，拓宽了我们对m6A识别蛋白的机制和功能的认识。Epi老师相信这个新发现会让m6A研究进一步升温！上图为3类m6A识别(reader)蛋白。a, 第一类，YTH结构域(蓝色显示)蛋白，与m6A(红色显示)直接结合。b, 第二类，利用m6A开关机制与含m6A的转录本结合：RNA的m6A修饰会破坏碱基互补配对，提高单链RNA基序的可进入性，从而被m6A识别蛋白识别(绿色显示)。RNA基序可以与m6A位点重叠。这类识别蛋白有hnRNPC、hnRNPG，hnRNPA2B1也可能属于这类蛋白。c, 此研究新发现的一类识别蛋白，利用共有的RNA结合结构域(RBD)及其侧翼区(绿色显示)来识别含m6A的转录本。这类识别蛋白包括IGF2BP，利用KH结构域及侧翼区来选择性结合含m6A的RNA；hnRNPA2B1也有可能属于这类蛋白，它的RRM及侧翼区可能有助于m6A选择。原文: Huang H, et al. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018 Mar;20(3):285-295. PMID: 29476152杨建华教授个人简介杨建华教授，中山大学博士生导师，长期致力于开发新算法、平台和实验方法研究非编码RNA基因和RNA修饰及其互作蛋白的结构、功能和作用机制。以通讯作者或第一作者身份在Nature Cell Biology、Cell Research、Nucleic Acids Res.、Cell Reports等杂志发表20多篇研究论文，以合作者身份在Nature Methods、Cell Stem Cell等杂志发表10多篇研究论文。开发starBase、starScan、snoSeeker和ChIPBase等工具被Nature等杂志引用超过1200次，受邀在Springer出版社出版了3篇关于非编码RNA研究方法的论著章节。目前担任Non-coding RNA杂志的编委。编辑于 2018-04-16 10:06核糖核酸（RNA）表观遗传学生物信息学赞同 17添加评论分享喜欢收藏申请

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N6-甲基腺苷（m6A）主要阅读器：癌症中的YTH家族蛋白,Frontiers in Oncology - X-MOL

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N6-甲基腺苷（m6A）主要阅读器：癌症中的YTH家族蛋白

Frontiers in Oncology

(

4.7

)

Pub Date : 2021-03-17

, DOI:

10.3389/fonc.2021.635329

Xin-Yuan Dai

Liang Shi

Zhi Li

Hai-Yan Yang

Ji-Fu Wei

Qiang Ding

在150多种RNA修饰中，N6-甲基腺苷（m6A）是真核RNA中最丰富的内部修饰，不仅在信使RNA中，而且在微RNA和长的非编码RNA中。它是哺乳动物细胞中一个动态且可逆的过程，由“写入器”安装，由METTL3，METTL14，WTAP，RBM15 / 15B和KIAA1429组成，并由“擦除器”删除，包括FTO和ALKBH5。此外，m6A修改被“读取器”识别，这些读取器在执行m6A功能中起着关键作用。IYT521-B同源性（YTH）家族蛋白是最早鉴定出的m6A阅读器蛋白。据报道，它们通过调节靶向RNA的代谢，包括RNA剪接，RNA输出，翻译和降解，参与癌症的发生和发展。关于m6A的功能及其在各种疾病中的作用有许多评论。但是，仅针对m6A读者的评论很少，尤其是YTH家族蛋白。在这篇综述中，我们系统地总结了YTH家族蛋白的结构和生物学功能的最新进展，以及它们在人类癌症中的作用以及在癌症治疗中的潜在应用。

"点击查看英文标题和摘要"

Main N6-methyladenosine (m6A) readers: YTH family proteins in cancers

Among the over 150 RNA modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, not only in messenger RNAs, but also in microRNAs and long non-coding RNAs. It is a dynamic and reversible process in mammalian cells, which is installed by “writers”, consisting of METTL3, METTL14, WTAP, RBM15/15B, and KIAA1429 and removed by “erasers”, including FTO and ALKBH5. Moreover, m6A modification is recognized by “readers”, which play the key role in executing m6A functions. IYT521-B homology (YTH) family proteins are the first identified m6A reader proteins. They were reported to participate in cancer tumorigenesis and development through regulating the metabolism of targeted RNAs, including RNA splicing, RNA export, translation, and degradation. There are many reviews about function of m6A and its role in various diseases. However, reviews only focusing on m6A readers, especially YTH family proteins are few. In this review, we systematically summarize the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and potential application in cancer therapy.

更新日期：2021-03-17

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m6A阅读者YTH蛋白的研究进展

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English

浙江农业科学 ›› 2021, Vol. 62 ›› Issue (2): 401-411.DOI: 10.16178/j.issn.0528-9017.20210251

• 食品技术 •

m6A阅读者YTH蛋白的研究进展

王晓乐(), 马荣荣, 鲁镇飞, 马炜炜*()

宁波市农业科学研究院作物研究所,浙江宁波 315000

收稿日期:2020-12-22

出版日期:2021-02-11

发布日期:2021-02-04

通讯作者:

马炜炜

作者简介:*马炜炜(1986—),男,助理研究员,博士,主要从事杂交水稻杂种优势分子机理及分子育种研究,E-mail: jonathan_@163.com。王晓乐(1985—),女,助理研究员,博士,主要从事杂交水稻分子育种研究工作,E-mail: 35337650@qq.com。

基金资助:宁波市自然基金(2018A610214);宁波市四大创新团队(2019CXGC001)

Received:2020-12-22

Online:2021-02-11

Published:2021-02-04

RichHTML

PDF (PC)

746

可视化

摘要/Abstract

摘要：甲基化是最为广泛存在的真核生物RNA转录后修饰形式。N6-甲基腺苷(m6A)对真核生物基因转录后调控至关重要,近年来的研究揭示m6A通过招募m6A结合蛋白从而影响包括器官建成、肿瘤形成、节律钟调控及X染色体沉默在内的多种生物学进程。YTH蛋白是目前研究最为深入的m6A结合蛋白,本文从YTH蛋白的分类、识别m6A的分子机理及其生物学功能3个方面详尽阐述了真核生物中存在的多样化的YTH蛋白如何影响具有m6A修饰的RNA的命运,以及如何调控生物体生长发育。最后,讨论了目前YTH蛋白研究仍有待解决的问题,展望了其在药物研发、作物育种等领域中的应用价值。

关键词:

N6-甲基腺苷,

YTH蛋白,

分类,

分子机理,

生物学功能

中图分类号:

Q756

引用本文

王晓乐, 马荣荣, 鲁镇飞, 马炜炜. m6A阅读者YTH蛋白的研究进展[J]. 浙江农业科学, 2021, 62(2): 401-411.

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YTH 是什么意思?

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首字母缩写词定义YTH为什么地狱吗？YTH汤普森，马尼托巴，加拿大-汤普森YTH酵母双杂交YTH青年

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tokenpocket钱包官网下|yth

tokenpocket钱包官网下|yth

云天化集团有限责任公司官网、云天化集团、云天化,化肥,有机化工,玻纤新材料,盐及盐化工,精细磷化工

Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics | Cell Death & Disease

YTH N6-甲基腺苷 RNA 结合蛋白 2（YTHDF2）基因 | MCE

NCB: 一种新的m6A阅读器！可促进mRNA翻译和稳定性 - 知乎

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N6-甲基腺苷（m6A）主要阅读器：癌症中的YTH家族蛋白,Frontiers in Oncology - X-MOL

YTH是什么意思? - YTH的全称 | 在线英文缩略词查询

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tokenpocket钱包官网下|yth

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云天化集团有限责任公司官网、云天化集团、云天化,化肥,有机化工,玻纤新材料,盐及盐化工,精细磷化工

Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics | Cell Death & Disease

YTH N6-甲基腺苷 RNA 结合蛋白 2（YTHDF2）基因 | MCE

NCB: 一种新的m6A阅读器！可促进mRNA翻译和稳定性 - 知乎

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N6-甲基腺苷（m6A）主要阅读器：癌症中的YTH家族蛋白,Frontiers in Oncology - X-MOL

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