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Understanding m6A Function Through Uncovering the Diversity Roles of YTH Domain-Containing Proteins

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Abstract

N6-methyladenosine (m6A) is the most abundant—internal modification of eukaryotic mRNA. m6A can be installed and removed by specific enzymes. The “writer,” “eraser,” and “reader” of m6A modification have been reported. These discoveries facilitate our understanding of the functional significance of m6A. m6A plays an essential role in diverse biological processes by recruiting the corresponding YTH domain-containing proteins, as well as recruiting additional translation initiation factors. Here, we provide an update on the various aspects of YTH domain-containing proteins, including an introduction to the YTH domain, the categories, distribution in cells, and biological roles of YTH proteins. Then we focus on the mechanisms that YTH proteins recognize m6A and mediate the fate of methylated-RNAs in eukaryotic cells.

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References

  1. Fu, Y., Dominissini, D., Rechavi, G., & He, C. (2014). Gene expression regulation mediated through reversible m6A RNA methylation. Nature Reviews Genetics, 15, 293–306.

    Article  CAS  PubMed  Google Scholar 

  2. Wu, R., Jiang, D., Wang, Y., & Wang, X. (2016). N6-methyladenosine m6A methylation in mRNA with a dynamic and reversible epigenetic modification. Molecular Biotechnology, 58, 450–459.

    Article  CAS  PubMed  Google Scholar 

  3. Adams, J. M., & Cory, S. (1975). Modified nucleosides and bizarre 5′-termini in mouse myeloma messenger-RNA. Nature, 255, 28–33.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Krug, R. M., Morgan, M. A., & Shatkin, A. J. (1976). Influenza viral mRNA contains internal N6-methyladenosine and 5′-terminal 7-methylguanosine in cap structures. Journal of Virology, 20, 45–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Jia, G. F., Fu, Y., Zhao, X., Dai, Q., et al. (2011). N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nature Chemical Biology, 7, 885–887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., et al. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-sEq. Nature, 485, 201–206.

    Article  CAS  PubMed  Google Scholar 

  8. Meyer, K. D., Saletore, Y., Zumbo, P., Elemento, O., et al. (2012). Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell, 149, 1635–1646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Roundtree, I. A., & He, C. (2016). Nuclear m6A reader YTHDC1 regulates mRNA splicing. Trends Genetics, 32, 320–321.

    Article  CAS  Google Scholar 

  10. Cui, Q., Shi, H. L., Ye, P., Li, L., et al. (2017). m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Reports, 18, 2622–2634.

    Article  CAS  PubMed  Google Scholar 

  11. Xiang, Y., Laurent, B., Hsu, C. H., Nachtergaele, S., et al. (2017). RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature, 543, 573–576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee, A. S., Kranzusch, P. J., & Cate, J. H. (2015). eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature, 522, 111–114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang, X., Zhao, B. S., Roundtree, I. A., Lu, Z., et al. (2015). N6-methyladenosine modulates messenger RNA translation efficiency. Cell, 161, 1388–1399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang, X., Lu, Z., Gomez, A., Hon, G. C., et al. (2014). N6-methyladenosine-dependent regulation of messenger RNA stability. Nature, 505, 117–120.

    Article  CAS  PubMed  Google Scholar 

  15. Desrosiers, R., Friderici, K., & Rottman, F. (1974). Identification of methylated nucleosides in messenger-RNA from Novikoff hepatoma-cells. Proceedings of the National Academy of Sciences USA, 71, 3971–3975.

    Article  CAS  Google Scholar 

  16. Batista, P. J., Molinie, B., Wang, J., Qu, K., et al. (2014). m6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell, 15, 707–719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Molinie, B., Wang, J., Lim, K. S., Hillebrand, R., et al. (2016). m6A-LAIC-seq reveals the census and complexity of the m6A epitranscriptome. Nature Methods, 13, 692–698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu, J., Yue, Y., Han, D., Wang, X., et al. (2014). A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nature Chemical Biology, 10, 93–95.

    Article  CAS  PubMed  Google Scholar 

  19. Ping, X. L., Sun, B. F., Wang, L., Xiao, W., et al. (2014). Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Research, 24, 177–189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zheng, G. Q., Dahl, J. A., Niu, Y. M., Fedorcsak, P., et al. (2013). ALKBH5 Is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Molecular Cell, 49, 18–29.

    Article  CAS  PubMed  Google Scholar 

  21. Narayan, P., & Rottman, F. M. (1988). An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Science, 242, 1159–1162.

    Article  CAS  PubMed  Google Scholar 

  22. Bokar, J. A., Rath-Shambaugh, M. E., Ludwiczak, R., Narayan, P., et al. (1994). Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. Journal of Biological Chemistry, 269, 17697–17704.

    CAS  PubMed  Google Scholar 

  23. Bokar, J. A., Shambaugh, M. E., Polayes, D., Matera, A. G., et al. (1997). Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA, 3, 1233–1247.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang, X., Feng, J., Xue, Y., Guan, Z., et al. (2017). Corrigendum: Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex. Nature, 542, 260.

    Article  CAS  PubMed  Google Scholar 

  25. Wang, P., Doxtader, K. A., & Nam, Y. (2016). Basis for Cooperative function of Mettl3 and Mettl14 methyltransferases. Molecular Cell, 63, 306–317. Structural.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang, Y., Li, Y., Toth, J. I., Petroski, M. D., et al. (2014). N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nature Cell Biology, 16, 191–198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Geula, S., Moshitch-Moshkovitz, S., Dominissini, D., Mansour, A. A., et al. (2015). m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science, 347, 1002–1006.

    Article  CAS  PubMed  Google Scholar 

  28. Gerken, T., Girard, C. A., Tung, Y. C., Webby, C. J., et al. (2007). The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science, 318, 1469–1472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., et al. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316, 889–894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Scuteri, A., Sanna, S., Chen, W. M., Uda, M., et al. (2010). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genetics. https://doi.org/10.1371/journal.pgen.0030115.

    Article  Google Scholar 

  31. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.

    Article  CAS  PubMed  Google Scholar 

  32. Jaffrey, S. R., & Kharas, M. G. (2017). Emerging links between m6A and misregulated mRNA methylation in cancer. Genome Medicine, 9, 2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, S. W., Sun, C. X., Li, J. H., Zhang, E. B., et al. (2017). Roles of RNA methylation by means of N6-methyladenosine in human cancers. Cancer Letters, 408, 112–120.

    Article  CAS  PubMed  Google Scholar 

  34. Fustin, J. M., Doi, M., Yamaguchi, Y., Hida, H., et al. (2013). RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell, 155, 793–806.

    Article  CAS  PubMed  Google Scholar 

  35. Akhtar, R. A., Reddy, A. B., Maywood, E. S., Clayton, J. D., et al. (2002). Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Current Biology, 12, 540–550.

    Article  CAS  PubMed  Google Scholar 

  36. Koike, N., Yoo, S. H., Huang, H. C., Kumar, V., et al. (2012). Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science, 338, 349–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kennedy, E. M., Bogerd, H. P., Kornepati, A. V. R., Kang, D., et al. (2017). Posttranscriptional m6A editing of HIV-1 mRNAs enhances viral gene expression (vol 19, pg 675, 2016). Cell Host & Microbe, 22, 830–830.

    Article  CAS  Google Scholar 

  38. Brocard, M., Ruggieri, A., & Locker, N. (2017). m6A RNA methylation, a new hallmark in virus-host interactions. Journal of General Virology, 98, 2207–2214.

    Article  CAS  PubMed  Google Scholar 

  39. Li, H. B., Tong, J. Y., Zhu, S., Batista, P. J., et al. (2017). m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature, 548, 338–342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li, L. J., Fan, Y. G., Leng, R. X., Pan, H. F., et al. (2018). Potential link between m6A modification and systemic lupus erythematosus. Molecular Immunology, 93, 55–63.

    Article  CAS  PubMed  Google Scholar 

  41. Kan, L., Grozhik, A. V., Vedanayagam, J., Patil, D. P., et al. (2017). The m6A pathway facilitates sex determination in Drosophila. Nature Communications, 8, 15737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Haussmann, I. U., Bodi, Z., Sanchez-Moran, E., Mongan, N. P., et al. (2016). m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature, 540, 301–304.

    Article  CAS  PubMed  Google Scholar 

  43. Roost, C., Lynch, S. R., Batista, P. J., Qu, K., et al. (2015). Correction to “structure and thermodynamics of N6-methyladenosine in RNA: A spring-loaded base modification”. Journal of the American Chemical Society, 137, 8308.

  44. Imai, Y., Matsuo, N., Ogawa, S., Tohyama, M., et al. (1998). Cloning of a gene, YT521, for a novel RNA splicing-related protein induced by hypoxia/reoxygenation. Molecular Brain Research, 53, 33–40.

    Article  CAS  PubMed  Google Scholar 

  45. Hartmann, A. M., Nayler, O., Schwaiger, F. W., Obermeier, A., et al. (1999). 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). Molecular Biology of the Cell, 10, 3909–3926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Xu, C., Wang, X., Liu, K., Roundtree, I. A., et al. (2015). Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain (vol 10, pg 927, 2014). Nature Chemical Biology, 11, 815.

    Article  CAS  PubMed  Google Scholar 

  47. Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., et al. (1997). Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Research, 25, 3389–3402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Stoilov, P., Rafalska, I., & Stamm, S. (2002). YTH: A new domain in nuclear proteins. Trends in Biochemical Sciences, 27, 495–497.

    Article  CAS  PubMed  Google Scholar 

  49. Hoffman, D. W., Query, C. C., Golden, B. L., White, S. W., et al. (1991). RNA-binding domain of the A protein component of the U1 small nuclear ribonucleoprotein analyzed by NMR spectroscopy is structurally similar to ribosomal proteins. Proceedings of the National Academy of Sciences USA, 88, 2495–2499.

    Article  CAS  Google Scholar 

  50. Luo, S. K., & Tong, L. (2014). Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proceedings of the National Academy of Sciences USA, 111, 13834–13839.

    Article  CAS  Google Scholar 

  51. Zhu, T., Roundtree, I. A., Wang, P., Wang, X., et al. (2014). Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell Research, 24, 1493–1496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Theler, D., Dominguez, C., Blatter, M., Boudet, J., et al. (2014). Solution structure of the YTH domain in complex with N6-methyladenosine RNA: A reader of methylated RNA. Nucleic Acids Research, 42, 13911–13919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li, F., Zhao, D., Wu, J., & Shi, Y. (2014). Structure of the YTH domain of human YTHDF2 in complex with an m6A mononucleotide reveals an aromatic cage for m6A recognition. Cell Research, 24, 1490–1492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yang, X., Li, H., Huang, Y., & Liu, S. (2013). The dataset for protein-RNA binding affinity. Protein Sci, 22, 1808–1811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Mauer, J., Luo, X., Blanjoie, A., Jiao, X., et al. (2017). Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature, 541, 371–375.

    Article  CAS  PubMed  Google Scholar 

  56. Wei, C. M., & Moss, B. (1975). Methylated nucleotides block 5′-terminus of vaccinia virus messenger RNA. Proceedings of the National Academy of Sciences USA, 72, 318–322.

    Article  CAS  Google Scholar 

  57. Patil, D. P., Chen, C. K., Pickering, B. F., Chow, A., et al. (2016). m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature, 537, 369–373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Dai, X. X., Wang, T. L., Gonzalez, G., & Wang, Y. S. (2018). Identification of YTH domain-containing proteins as the readers for N1-methyladenosine in RNA. Analytical Chemistry, 90, 6380–6384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Safra, M., Sas-Chen, A., Nir, R., Winkler, R., et al. (2017). The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature, 551, 251.

    Article  CAS  PubMed  Google Scholar 

  60. Dominissini, D., Nachtergaele, S., Moshitch-Moshkovitz, S., Peer, E., et al. (2016). The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA. Nature, 530, 441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Oates, M. E., Romero, P., Ishida, T., Ghalwash, M., et al. (2013). (DP2)-P-2: Database of disordered protein predictions. Nucleic Acids Research, 41, D508–D516.

    Article  CAS  PubMed  Google Scholar 

  62. Du, H., Zhao, Y., He, J. Q., Zhang, Y., et al. (2016). YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nature Communications, 7, 12626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lichinchi, G., Gao, S., Saletore, Y., Gonzalez, G. M., et al. (2016). Dynamics of the human and viral m6A RNA methylomes during HIV-1 infection of T cells. Nature Microbiology, 1, 16011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tanabe, A., Tanikawa, K., Tsunetomi, M., Takai, K., et al. (2016). RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1 alpha mRNA is translated. Cancer Letter, 376, 34–42.

    Article  CAS  Google Scholar 

  65. Meyer, K. D., Patil, D. P., Zhou, J., Zinoviev, A., et al. (2015). 5′ UTR m6A promotes cap-independent translation. Cell, 163, 999–1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Alarcon, C. R., Goodarzi, H., Lee, H., Liu, X. H., et al. (2015). HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events. Cell, 162, 1299–1308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chen, K., Lu, Z., Wang, X., Fu, Y., et al. (2015). High-resolution N6-methyladenosine map using photo-crosslinking-assisted m6A sequencing. Angewandte Chemie International Edition, 54, 1587–1590.

    Article  CAS  Google Scholar 

  68. Wu, B. X., Su, S. C., Patil, D. P., Liu, H. H., et al. (2018). Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nature Communications, 9, 420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Huang, H., Weng, H., Sun, W., Qin, X., et al., (2018). Author Correction: Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nature Cell Biology, 20, 285–295.

    Google Scholar 

  70. Li, D. Y., Zhang, H. J., Hong, Y. B., Huang, L., et al. (2014). Genome-wide identification, biochemical characterization, and expression analyses of the YTH domain-containing RNA-binding protein family in Arabidopsis and rice. Plant Molecular Biology Reporter, 32, 1169–1186.

    Article  CAS  Google Scholar 

  71. Reichel, M., Liao, Y., Rettel, M., Ragan, C., et al. (2016). In planta determination of the mRNA-binding proteome of Arabidopsis etiolated seedlings. The Plant Cell, 28, 2435–2452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Arribas-Hernandez, L., Bressendorff, S., Hansen, M. H., Poulsen, C., et al. (2018). An m6A-YTH module controls developmental timing and morphogenesis in Arabidopsis. The Plant Cell, 30, 952–967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tirumuru, N., Zhao, B. S., Lu, W. X., Lu, Z. K., et al., (2016). N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression. Elife, 5, e15528.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Nguyen, T. T., Ma, L. N., Slovak, M. L., Bangs, C. D., et al. (2006). Identification of novel Runx1 (AML1) translocation partner genes SH3D19, YTHDF2, and ZNF687 in acute myeloid leukemia. Genes Chromosomes Cancer, 45, 918–932.

    Article  CAS  PubMed  Google Scholar 

  75. Zhou, J., Wan, J., Gao, X., Zhang, X., et al. (2015). Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature, 526, 591–594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wang, X., Sun, B., Jiang, Q. (2018). mRNA m6A plays opposite role in regulating UCP2 and PNPLA2 protein expression in adipocytes. International Journal of Obesity, 42, 1912–1924.

    Google Scholar 

  77. Wu, R., Yao, Y., Jiang, Q., Cai, M., et al. (2018). Epigallocatechin gallate targets FTO and inhibits adipogenesis in an mRNA m6A-YTHDF2-dependent manner. International Journal of Obesity (London), 42, 1378–1388.

    Article  CAS  Google Scholar 

  78. Zhao, B. S., Wang, X., Beadell, A. V., Lu, Z., et al. (2017). m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature, 542, 475–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wei, L. H., Song, P. Z., Wang, Y., Lu, Z. K., et al. (2018). The m6A reader ECT2 controls trichome morphology by affecting mRNA stability in Arabidopsis. The Plant Cell, 30, 968–985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Scutenaire, J., Deragon, J. M., Jean, V., Benhamed, M., et al. (2018). The YTH domain protein ECT2 is an m6A reader required for normal trichome branching in Arabidopsis. The Plant Cell, 30, 986–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hsu, P. J., Zhu, Y. F., Ma, H. H., Guo, Y. H., et al. (2017). YTHDC2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Research, 27, 1115–1127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jain, D., Puno, M. R., Meydan, C., Lailler, N., et al. (2018). ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2. Elife, 7, e30919.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Drayman, N., Karin, O., Mayo, A., Danon, T., et al. (2017). Dynamic proteomics of herpes simplex virus infection. MBio. https://doi.org/10.1128/mBio.01612-17.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Ma, S., Menon, R., Poulos, R. C., & Wong, J. W. H. (2017). Proteogenomic analysis prioritises functional single nucleotide variants in cancer samples. Oncotarget, 8, 95841–95852.

    PubMed  PubMed Central  Google Scholar 

  85. Shichino, Y., Otsubo, Y., Kimori, Y., Yamamoto, M., et al. (2018). YTH-RNA-binding protein prevents deleterious expression of meiotic proteins by tethering their mRNAs to nuclear foci. Elife. https://doi.org/10.7554/eLife.32155.001.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Shi, H. L., Wang, X., Lu, Z. K., Zhao, B. X. S., et al. (2017). YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Research, 27, 315–328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Hubstenberger, A., Courel, M., Benard, M., Souquere, S., et al. (2017). P-body purification reveals the condensation of repressed mRNA regulons. Molecular Cell, 68, 144–157 e5.

    Article  CAS  PubMed  Google Scholar 

  88. Li, A., Chen, Y. S., Ping, X. L., Yang, X., et al. (2017). Cytoplasmic m6A reader YTHDF3 promotes mRNA translation. Cell Research, 27, 444–447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zhang, Z. Y., Theler, D., Kaminska, K. H., Hiller, M., et al. (2010). The YTH domain is a novel RNA binding domain. Journal of Biological Chemistry, 285, 14701–14710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ke, S. D., Pandya-Jones, A., Saito, Y., Fak, J. J., et al. (2017). m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes & Development, 31, 990–1006.

    Article  CAS  Google Scholar 

  91. Engreitz, J. M., Pandya-Jones, A., McDonel, P., Shishkin, A., et al. (2013). The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science, 341,1237973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kretschmer, J., Rao, H., Hackert, P., Sloan, K. E., et al. (2018). The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5′-3′ exoribonuclease XRN1. RNA, 24, 1339–1350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Tanabe, A., Konno, J., Tanikawa, K., & Sahara, H. (2014). Transcriptional machinery of TNF-alpha-inducible YTH domain containing 2 (YTHDC2) gene. Gene, 535, 24–32.

    Article  CAS  PubMed  Google Scholar 

  94. Hornbeck, P. V., Zhang, B., Murray, B., Kornhauser, J. M., et al. (2015). PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Research, 43, D512–D520.

    Article  CAS  PubMed  Google Scholar 

  95. Kato, M., Han, T. N. W., Xie, S. H., Shi, K., et al. (2012). Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell, 149, 753–767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Thinon, E., Serwa, R. A., Broncel, M., Brannigan, J. A., et al. (2014). Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nature Communications, 5, 4919.

    Article  CAS  PubMed  Google Scholar 

  97. Lichinchi, G., Zhao, B. S., Wu, Y. A., Lu, Z. K., et al. (2016). Dynamics of human and viral RNA methylation during zika virus infection. Cell Host & Microbe, 20, 666–673.

    Article  CAS  Google Scholar 

  98. Gokhale, N. S., McIntyre, A. B. R., McFadden, M. J., Roder, A. E., et al. (2016). N6-methyladenosine in flaviviridae viral RNA genomes regulates infection. Cell Host & Microbe, 20, 654–665.

    Article  CAS  Google Scholar 

  99. Dixit, D., Xie, Q., Rich, J. N., & Zhao, J. C. (2017). Messenger rna methylation regulates glioblastoma tumorigenesis. Cancer Cell, 31, 474–475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Zhang, S. C., Zhao, B. S., Zhou, A. D., Lin, K. Y., et al. (2017). m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell, 31, 591–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kwok, C. T., Marshall, A. D., Rasko, J. E. J., & Wong, J. J. L. (2017). Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia (vol 10, 39, 2017). Journal of Hematology & Oncology, 10, 39.

    Article  CAS  Google Scholar 

  102. Canaani, D., Kahana, C., Lavi, S., & Groner, Y. (1979). Identification and mapping of N6-methyladenosine containing sequences in Simian Virus-40 RNA. Nucleic Acids Research, 6, 2879–2899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 31572413), the Natural Science Foundation of Zhejiang Province (No. LZ17C170001), the State Key Program of National Natural Science Foundation of China (No. 3163000269), and the Special Fund for Cultivation and Breeding of New Transgenic Organism (No. 2014ZX0800949B).

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  1. College of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China

    Y. L. Zhao, Y. H. Liu, R. F. Wu, Z. Bi, Y. X. Yao, Q. Liu, Y. Z. Wang & X. X. Wang

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  1. Y. L. Zhao
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  2. Y. H. Liu
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  4. Z. Bi
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Correspondence to X. X. Wang.

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Zhao, Y.L., Liu, Y.H., Wu, R.F. et al. Understanding m6A Function Through Uncovering the Diversity Roles of YTH Domain-Containing Proteins. Mol Biotechnol 61, 355–364 (2019). https://doi.org/10.1007/s12033-018-00149-z

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