Post-transcriptional modifications in development and stem cells

Development (Cambridge)

Volumn 143, Issue 21, 2016, Pages 3871-3881

  Frye, Michaela ^a   Blanco, Sandra ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b CIC BIOGUNE   (Spain)

Author keywords

5 methylcytosine; N6 methyladenosine; Post transcriptional modifications; Pseudouridylation; RNA methylation; Stem cells

Indexed keywords

5 METHYLCYTOSINE; 6 N METHYLADENOSINE; ADENOSINE; CYTOSINE; GUIDE RNA; MESSENGER RNA; MICRORNA; PSEUDOURIDINE; RNA BINDING PROTEIN; TRANSFER RNA; UNTRANSLATED RNA; RNA;

CATALYSIS; CELL FATE; CELL MATURATION; CHEMICAL MODIFICATION; EMBRYONIC STEM CELL; GENE FUNCTION; GENETIC VARIABILITY; HUMAN; LOSS OF FUNCTION MUTATION; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REVIEW; RNA METHYLATION; RNA PROCESSING; RNA TRANSLATION; STEM CELL SELF-RENEWAL; TRANSLATION INITIATION; ADULT; ADULT STEM CELL; ANIMAL; CELL DIFFERENTIATION; CELL SELF-RENEWAL; EMBRYO DEVELOPMENT; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PHYSIOLOGY; STEM CELL;

ADULT; ADULT STEM CELLS; ANIMALS; CELL DIFFERENTIATION; CELL SELF RENEWAL; EMBRYONIC DEVELOPMENT; GROWTH AND DEVELOPMENT; HUMANS; RNA; RNA PROCESSING, POST-TRANSCRIPTIONAL; STEM CELLS;

EID: 84994236488     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.136556     Document Type: Review

References (114)

1. Abbasi-Moheb, L., Mertel, S., Gonsior, M., Nouri-Vahid, L., Kahrizi, K., Cirak, S., Wieczorek, D., Motazacker, M. M., Esmaeeli-Nieh, S., Cremer, K. et al. (2012). Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am. J. Hum. Genet. 90, 847-855.
2. Agarwal, S., Loh, Y.-H., McLoughlin, E. M., Huang, J., Park, I.-H., Miller, J. D., Huo, H., Okuka, M., dos Reis, R. M., Loewer, S. et al. (2010). Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464, 292-296.
3. Aguilo, F., Li, S. D., Balasubramaniyan, N., Sancho, A., Benko, S., Zhang, F., Vashisht, A., Rengasamy, M., Andino, B., Chen, C. H. et al. (2016). Deposition of 5-methylcytosine on enhancer RNAs enables the coactivator function of PGC- 1alpha. Cell Rep. 14, 479-492.
4. Alarcon, C. R., Goodarzi, H., Lee, H., Liu, X., Tavazoie, S. and Tavazoie, S. F. (2015a). HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell 162, 1299-1308.
5. Alarcon, C. R., Lee, H., Goodarzi, H., Halberg, N. and Tavazoie, S. F. (2015b). N6- methyladenosine marks primary microRNAs for processing. Nature 519, 482-485.
6. Alazami, A. M., Hijazi, H., Al-Dosari, M. S., Shaheen, R., Hashem, A., Aldahmesh, M. A., Mohamed, J. Y., Kentab, A., Salih, M. A., Awaji, A. et al. (2013). Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus. J. Med. Genet. 7, 425-430.
7. Anderson, J., Phan, L., Cuesta, R., Carlson, B. A., Pak, M., Asano, K., Bjork, G. R., Tamame, M. and Hinnebusch, A. G. (1998). The essential Gcd10p- Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA. Genes Dev. 12, 3650-3662.
8. Anderson, B. R., Muramatsu, H., Nallagatla, S. R., Bevilacqua, P. C., Sansing, L. H., Weissman, D. and Kariko, K. (2010). Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38, 5884-5892.
9. Batista, L. F. Z., Pech, M. F., Zhong, F. L., Nguyen, H. N., Xie, K. T., Zaug, A. J., Crary, S. M., Choi, J., Sebastiano, V., Cherry, A. et al. (2011). Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474, 399-402.
10. Batista, P. J., Molinie, B., Wang, J., Qu, K., Zhang, J., Li, L., Bouley, D. M., Lujan, E., Haddad, B., Daneshvar, K. et al. (2014). m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15, 707-719.
11. Bellodi, C., McMahon, M., Contreras, A., Juliano, D., Kopmar, N., Nakamura, T., Maltby, D., Burlingame, A., Savage, S. A., Shimamura, A. et al. (2013). H/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation. Cell Rep. 3, 1493-1502.
12. Bentley, D. L. (2014). Coupling mRNA processing with transcription in time and space. Nat. Rev. Genet. 15, 163-175.
13. Blanco, S., Kurowski, A., Nichols, J., Watt, F. M., Benitah, S. A. and Frye, M. (2011). The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genet. 7, e1002403.
14. Blanco, S., Dietmann, S., Flores, J. V., Hussain, S., Kutter, C., Humphreys, P., Lukk, M., Lombard, P., Treps, L., Popis, M. et al. (2014). Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J. 33, 2020-2039.
15. Blanco, S., Bandiera, R., Popis, M., Hussain, S., Lombard, P., Aleksic, J., Sajini, A., Tanna, H., Cortes-Garrido, R., Gkatza, N. et al. (2016). Stem cell function and stress response are controlled by protein synthesis. Nature 534, 335-340.
16. Bodi, Z., Zhong, S., Mehra, S., Song, J., Graham, N., Li, H., May, S. and Fray, R. G. (2012). Adenosine methylation in Arabidopsis mRNA is associated with the 3’ end and reduced levels cause developmental defects. Front. Plant Sci. 3, 48.
17. Boissel, S., Reish, O., Proulx, K., Kawagoe-Takaki, H., Sedgwick, B., Yeo, G. S. H., Meyre, D., Golzio, C., Molinari, F., Kadhom, N. et al. (2009). Loss-offunction mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am. J. Hum. Genet. 85, 106-111.
18. Bokar, J. A., Shambaugh, M. E., Polayes, D., Matera, A. G. and Rottman, F. M. (1997). Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3, 1233-1247.
19. Buszczak, M., Signer, R. A. J. and Morrison, S. J. (2014). Cellular differences in protein synthesis regulate tissue homeostasis. Cell 159, 242-251.
20. Carlile, T. M., Rojas-Duran, M. F., Zinshteyn, B., Shin, H., Bartoli, K. M. and Gilbert, W. V. (2014). Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515, 143-146.
21. Chan, C. T. Y., Pang, Y. L. J., Deng, W., Babu, I. R., Dyavaiah, M., Begley, T. J. and Dedon, P. C. (2012). Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins. Nat. Commun. 3, 937.
22. Charette, M. and Gray, M.W. (2000). Pseudouridine in RNA: what, where, how, and why. IUBMB Life 49, 341-351.
23. Chen, J.-L., Opperman, K. K. and Greider, C. W. (2002). A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA. Nucleic Acids Res. 30, 592-597.
24. Chen, T., Hao, Y.-J., Zhang, Y., Li, M.-M., Wang, M., Han, W., Wu, Y., Lv, Y., Hao, J., Wang, L. et al. (2015). m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 16, 289-301.
25. Chi, L. and Delgado-Olguin, P. (2013). Expression of NOL1/NOP2/sun domain (Nsun) RNA methyltransferase family genes in early mouse embryogenesis. Gene Expr. Patterns 13, 319-327.
26. Davarniya, B., Hu, H., Kahrizi, K., Musante, L., Fattahi, Z., Hosseini, M., Maqsoud, F., Farajollahi, R., Wienker, T. F., Ropers, H. H. et al. (2015). The role of a novel TRMT1 gene mutation and rare GRM1 gene defect in intellectual disability in two Azeri families. PLoS ONE 10, e0129631.
27. Davis, D. R. (1995). Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res. 23, 5020-5026.
28. Delatte, B., Wang, F., Ngoc, L. V., Collignon, E., Bonvin, E., Deplus, R., Calonne, E., Hassabi, B., Putmans, P., Awe, S. et al. (2016). RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science 351, 282-285.
29. Dina, C., Meyre, D., Gallina, S., Durand, E., Korner, A., Jacobson, P., Carlsson, L. M. S., Kiess, W., Vatin, V., Lecoeur, C. et al. (2007). Variation in FTO contributes to childhood obesity and severe adult obesity. Nat. Genet. 39, 724-726.
30. Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., Kupiec, M. et al. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201-206.
31. Duan, J., Li, L., Lu, J., Wang, W. and Ye, K. (2009). Structural mechanism of substrate RNA recruitment in H/ACA RNA-guided pseudouridine synthase. Mol. Cell 34, 427-439.
32. Dubnikov, T. and Cohen, E. (2015). Proteostasis collapse, inter-tissue communication, and the regulation of aging at the organismal level. Front. Genet. 6, 80.
33. Fischer, J., Koch, L., Emmerling, C., Vierkotten, J., Peters, T., Bruning, J. C. and Ruther, U. (2009). Inactivation of the Fto gene protects from obesity. Nature 458, 894-898.
34. Fong, Y. W., Ho, J. J., Inouye, C. and Tjian, R. (2014). The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells. Elife 3, e03573.
35. Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R. B., Elliott, K. S., Lango, H., Rayner, N. W. 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.
36. Freude, K., Hoffmann, K., Jensen, L. R., Delatycki, M. B., des Portes, V., Moser, B., Hamel, B., van Bokhoven, H., Moraine, C., Fryns, J. P. et al. (2004). Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. Am. J. Hum. Genet. 2, 305-309.
37. Fu, Y., Jia, G., Pang, X., Wang, R. N., Wang, X., Li, C. J., Smemo, S., Dai, Q., Bailey, K. A., Nobrega, M. A. et al. (2013). FTO-mediated formation of N6- hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat. Commun. 4, 1798.
38. Fu, L., Guerrero, C. R., Zhong, N., Amato, N. J., Liu, Y., Liu, S., Cai, Q., Ji, D., Jin, S.-G., Niedernhofer, L. J. et al. (2014). Tet-mediated formation of 5- hydroxymethylcytosine in RNA. J. Am. Chem. Soc. 136, 11582-11585.
39. Gambaryan, A. S., Venkstern, T. V. and Baev, A. A. (1976). Use of the method of mixed substrates to study the specificity of tRNA methylases. Molekuliarn. Biol. 10, 697-705.
40. Ge, J. and Yu, Y.-T. (2013). RNA pseudouridylation: new insights into an old modification. Trends Biochem. Sci. 38, 210-218.
41. Gebetsberger, J., Zywicki, M., Kunzi, A. and Polacek, N. (2012). tRNA-derived fragments target the ribosome and function as regulatory non-coding RNA in Haloferax volcanii. Archaea 2012, 260909.
42. Geula, S., Moshitch-Moshkovitz, S., Dominissini, D., Mansour, A. A., Kol, N., Salmon-Divon, M., Hershkovitz, V., Peer, E., Mor, N., Manor, Y. S. et al. (2015). Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347, 1002-1006.
43. Gingold, H., Tehler, D., Christoffersen, N. R., Nielsen, M. M., Asmar, F., Kooistra, S. M., Christophersen, N. S., Christensen, L. L., Borre, M., Sorensen, K. D. et al. (2014). A dual program for translation regulation in cellular proliferation and differentiation. Cell 158, 1281-1292.
44. Goll, M. G., Kirpekar, F., Maggert, K. A., Yoder, J. A., Hsieh, C.-L., Zhang, X., Golic, K. G., Jacobsen, S. E. and Bestor, T. H. (2006). Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311, 395-398.
45. Gu, B.-W., Fan, J.-M., Bessler, M. and Mason, P. J. (2011). Accelerated hematopoietic stem cell aging in a mouse model of dyskeratosis congenita responds to antioxidant treatment. Aging Cell 10, 338-348.
46. Haag, S., Warda, A. S., Kretschmer, J., Günnigmann, M. A., Höbartner, C. and Bohnsack, M. T. (2015). NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. RNA 21, 1532-1543.
47. Hamma, T. and Ferre-D’Amare, A. R. (2006). Pseudouridine synthases. Chem. Biol. 13, 1125-1135.
48. Harris, T., Marquez, B., Suarez, S. and Schimenti, J. (2007). Sperm motility defects and infertility in male mice with a mutation in Nsun7, a member of the Sun domain-containing family of putative RNA methyltransferases. Biol. Reprod. 77, 376-382.
49. He, J., Navarrete, S., Jasinski, M., Vulliamy, T., Dokal, I., Bessler, M. and Mason, P. J. (2002). Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenita, causes embryonic lethality in mice. Oncogene 21, 7740-7744.
50. Heiss, N. S., Knight, S. W., Vulliamy, T. J., Klauck, S. M., Wiemann, S., Mason, P. J., Poustka, A. and Dokal, I. (1998). X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat. Genet. 19, 32-38.
51. Honda, S., Hayashi, S., Imoto, I., Toyama, J., Okazawa, H., Nakagawa, E., Goto, Y. and Inazawa, J. (2010). Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis. J. Hum. Genet. 9, 590-599.
52. Hong, B., Brockenbrough, J. S., Wu, P. and Aris, J. P. (1997). Nop2p is required for pre-rRNA processing and 60S ribosome subunit synthesis in yeast. Mol. Cell. Biol. 17, 378-388.
53. Hongay, C. F. and Orr-Weaver, T. L. (2011). Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. Proc. Natl. Acad. Sci. USA 108, 14855-14860.
54. Horiuchi, K., Umetani, M., Minami, T., Okayama, H., Takada, S., Yamamoto, M., Aburatani, H., Reid, P. C., Housman, D. E., Hamakubo, T. et al. (2006). Wilms’ tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc. Natl. Acad. Sci. USA 103, 17278-17283.
55. Huber, S. M., van Delft, P., Mendil, L., Bachman, M., Smollett, K., Werner, F., Miska, E. A. and Balasubramanian, S. (2015). Formation and abundance of 5- hydroxymethylcytosine in RNA. Chembiochem 16, 752-755.
56. Hussain, S., Aleksic, J., Blanco, S., Dietmann, S. and Frye, M. (2013a). Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome Biol. 14, 215.
57. Hussain, S., Sajini, A. A., Blanco, S., Dietmann, S., Lombard, P., Sugimoto, Y., Paramor, M., Gleeson, J. G., Odom, D. T., Ule, J. et al. (2013b). NSun2- mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Rep. 4, 255-261.
58. Hussain, S., Tuorto, F., Menon, S., Blanco, S., Cox, C., Flores, J. V., Watt, S., Kudo, N. R., Lyko, F. and Frye, M. (2013c). The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation. Mol. Cell. Biol. 33, 1561-1570.
59. Igoillo-Esteve, M., Genin, A., Lambert, N., Désir, J., Pirson, I., Abdulkarim, B., Simonis, N., Drielsma, A., Marselli, L., Marchetti, P. et al. (2013). tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans. PLoS Genet. 10, e1003888.
60. Ivanov, P., Emara, M. M., Villen, J., Gygi, S. P. and Anderson, P. (2011). Angiogenin-induced tRNA fragments inhibit translation initiation. Mol. Cell 43, 613-623.
61. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.-G. et al. (2011). N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885-887.
62. Karijolich, J. and Yu, Y.-T. (2011). Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474, 395-398.
63. Kariko, K., Muramatsu, H., Welsh, F. A., Ludwig, J., Kato, H., Akira, S. and Weissman, D. (2008). Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833-1840.
64. Karlsborn, T., Tükenmez, H., Chen, C. and Byström, A. S. (2014). Familial dysautonomia (FD) patients have reduced levels of the modified wobble nucleoside mcm(5)s(2)U in tRNA. Biochem. Biophys. Res. Commun. 454, 441-445.
65. Kawai, G., Yamamoto, Y., Kamimura, T., Masegi, T., Sekine, M., Hata, T., Iimori, T., Watanabe, T., Miyazawa, T. and Yokoyama, S. (1992). Conformational rigidity of specific pyrimidine residues in tRNA arises from posttranscriptional modifications that enhance steric interaction between the base and the 2’- hydroxyl group. Biochemistry 31, 1040-1046.
66. Khan, M. A., Rafiq, M. A., Noor, A., Hussain, S., Flores, J. V., Rupp, V., Vincent, A. K., Malli, R., Ali, G., Khan, F. S. et al. (2012). Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. Am. J. Hum. Genet. 90, 856-863.
67. Khoddami, V. and Cairns, B. R. (2013). Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat. Biotechnol. 31, 458-464.
68. Khosronezhad, N., Colagar, A. H. and Jorsarayi, S. G. (2014). T26248Gtransversion mutation in exon7 of the putative methyltransferase Nsun7 gene causes a change in protein folding associated with reduced sperm motility in asthenospermic men. Reprod. Fertil. Dev. 27, 471-480.
69. King, T. H., Liu, B., McCully, R. R. and Fournier, M. J. (2003). Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center. Mol. Cell 11, 425-435.
70. Knight, S.W., Heiss, N. S., Vulliamy, T. J., Aalfs, C. M., McMahon, C., Richmond, P., Jones, A., Hennekam, R. C. M., Poustka, A., Mason, P. J. et al. (1999). Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1. Br. J. Haematol. 107, 335-339.
71. Komara, M., Al-Shamsi, A. M., Ben-Salem, S., Ali, B. R. and Al-Gazali, L. (2015). A novel single-nucleotide deletion (c.1020delA) in NSUN2 causes intellectual disability in an Emirati child. J. Mol. Neurosci. 57, 393-399.
72. Liang, X.-H., Liu, Q. and Fournier, M. J. (2007). rRNA modifications in an intersubunit bridge of the ribosome strongly affect both ribosome biogenesis and activity. Mol. Cell 28, 965-977.
73. Liang, B., Zhou, J., Kahen, E., Terns, R. M., Terns, M. P. and Li, H. (2009). Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA. Nat. Struct. Mol. Biol. 16, 740-746.
74. Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X. et al. (2014). A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93-95.
75. Liu, N., Dai, Q., Zheng, G., He, C., Parisien, M. and Pan, T. (2015). N(6)- methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518, 560-564.
76. Machnicka, M. A., Milanowska, K., Osman Oglou, O., Purta, E., Kurkowska, M., Olchowik, A., Januszewski, W., Kalinowski, S., Dunin-Horkawicz, S., Rother, K. M. et al. (2013). MODOMICS: a database of RNA modification pathways–2013 update. Nucleic Acids Res. 41, D262-D267.
77. Martinez, F. J., Lee, J. H., Lee, J. E., Blanco, S., Nickerson, E., Gabriel, S., Frye, M., Al-Gazali, L. and Gleeson, J. G. (2012). Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J. Med. Genet. 49, 380-385.
78. McMurray, F., Church, C. D., Larder, R., Nicholson, G., Wells, S., Teboul, L., Tung, Y. C. L., Rimmington, D., Bosch, F., Jimenez, V. et al. (2013). Adult onset global loss of the fto gene alters body composition and metabolism in the mouse. PLoS Genet. 9, e1003166.
79. Metodiev, M. D., Spahr, H., Loguercio Polosa, P., Meharg, C., Becker, C., Altmueller, J., Habermann, B., Larsson, N.-G. and Ruzzenente, B. (2014). NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet. 10, e1004110.
80. Meyer, K. D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C. E. and Jaffrey, S. R. (2012). Comprehensive analysis ofmRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell 149, 1635-1646.
81. Meyer, K. D., Patil, D. P., Zhou, J., Zinoviev, A., Skabkin, M. A., Elemento, O., Pestova, T. V., Qian, S.-B. and Jaffrey, S. R. (2015). 5’ UTR m(6)A promotes Cap-independent translation. Cell 163, 999-1010.
82. Mitchell, J. R., Wood, E. and Collins, K. (1999). A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402, 551-555.
83. Nakano, S., Suzuki, T., Kawarada, L., Iwata, H., Asano, K. and Suzuki, T. (2016). NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met). Nat. Chem. Biol. 12, 546-551.
84. Ozban, N., Tandler, J. and Sirlin, J. L. (1964). Methylation of nucleolar RNA during development of the amphibian ooecyte. J. Embryol. Exp. Morphol. 12, 373-380.
85. Patil, D. P., Chen, C. K., Pickering, B. F., Chow, A., Jackson, C., Guttman, M. and Jaffrey, S. R. (2016). m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537, 369-373.
86. Piekna-Przybylska, D., Przybylski, P., Baudin-Baillieu, A., Rousset, J.-P. and Fournier, M. J. (2008). Ribosome performance is enhanced by a rich cluster of pseudouridines in the A-site finger region of the large subunit. J. Biol. Chem. 283, 26026-26036.
87. Ping, X.-L., Sun, B.-F., Wang, L., Xiao, W., Yang, X., Wang, W.-J., Adhikari, S., Shi, Y., Lv, Y., Chen, Y.-S. et al. (2014). Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24, 177-189.
88. Rai, K., Chidester, S., Zavala, C. V., Manos, E. J., James, S. R., Karpf, A. R., Jones, D. A. and Cairns, B. R. (2007). Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes Dev. 21, 261-266.
89. Sampath, P., Pritchard, D. K., Pabon, L., Reinecke, H., Schwartz, S. M., Morris, D. R. and Murry, C. E. (2008). A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation. Cell Stem Cell 2, 448-460.
90. Schaefer, M., Pollex, T., Hanna, K., Tuorto, F., Meusburger, M., Helm, M. and Lyko, F. (2010). RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 24, 1590-1595.
91. Schosserer, M., Minois, N., Angerer, T. B., Amring, M., Dellago, H., Harreither, E., Calle-Perez, A., Pircher, A., Gerstl, M. P., Pfeifenberger, S. et al. (2015). Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat. Commun. 6, 6158.
92. Schwartz, S., Bernstein, D. A., Mumbach, M. R., Jovanovic, M., Herbst, R. H., Leon-Ricardo, B. X., Engreitz, J. M., Guttman, M., Satija, R., Lander, E. S. et al. (2014a). Transcriptome-wide mapping reveals widespread dynamicregulated pseudouridylation of ncRNA and mRNA. Cell 159, 148-162.
93. Schwartz, S., Mumbach, M. R., Jovanovic, M., Wang, T., Maciag, K., Bushkin, G. G., Mertins, P., Ter-Ovanesyan, D., Habib, N., Cacchiarelli, D. et al. (2014b). Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5’ sites. Cell Rep. 8, 284-296.
94. Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U. et al. (2007). A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341-1345.
95. Scuteri, A., Sanna, S., Chen, W. M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, M., Usala, G. et al. (2007). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 7, e115.
96. Shaheen, R., Abdel-Salam, G. M., Guy, M. P., Alomar, R., Abdel-Hamid, M. S., Afifi, H. H., Ismail, S. I., Emam, B. A., Phizicky, E. M. and Alkuraya, F. S. (2015). Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome Biol. 16, 210.
97. Sharma, S., Yang, J., Watzinger, P., Kotter, P. and Entian, K.-D. (2013). Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively. Nucleic Acids Res. 41, 9062-9076.
98. Shin, B.-S., Kim, J.-R., Walker, S. E., Dong, J., Lorsch, J. R. and Dever, T. E. (2011). Initiation factor eIF2gamma promotes eIF2-GTP-Met-tRNAi(Met) ternary complex binding to the 40S ribosome. Nat. Struct. Mol. Biol. 18, 1227-1234.
99. Signer, R. A. J., Magee, J. A., Salic, A. and Morrison, S. J. (2014). Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature 509, 49-54.
100. Smemo, S., Tena, J. J., Kim, K.-H., Gamazon, E. R., Sakabe, N. J., Gomez-Marin, C., Aneas, I., Credidio, F. L., Sobreira, D. R., Wasserman, N. F. et al. (2014). Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507, 371-375.
101. Spriggs, K. A., Bushell, M. and Willis, A. E. (2010). Translational regulation of gene expression during conditions of cell stress. Mol. Cell 40, 228-237.
102. Squires, J. E., Patel, H. R., Nousch, M., Sibbritt, T., Humphreys, D. T., Parker, B. J., Suter, C. M. and Preiss, T. (2012). Widespread occurrence of 5- methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 40, 5023-5033.
103. Tuorto, F., Liebers, R., Musch, T., Schaefer, M., Hofmann, S., Kellner, S., Frye, M., Helm, M., Stoecklin, G. and Lyko, F. (2012). RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat. Struct. Mol. Biol. 19, 900-905.
104. Tuorto, F., Herbst, F., Alerasool, N., Bender, S., Popp, O., Federico, G., Reitter, S., Liebers, R., Stoecklin, G., Grone, H.-J. et al. (2015). The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J. 34, 2350-2362.
105. Van Haute, L., Dietmann, S., Kremer, L., Hussain, S., Pearce, S. F., Powell, C. A., Rorbach, J., Lantaff, R., Blanco, S., Sauer, S. et al. (2016). Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat. Commun. 7, 12039.
106. Wang, X., Lu, Z., Gomez, A., Hon, G. C., Yue, Y., Han, D., Fu, Y., Parisien, M., Dai, Q., Jia, G. et al. (2014a). N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505, 117-120.
107. Wang, Y., Li, Y., Toth, J. I., Petroski, M. D., Zhang, Z. and Zhao, J. C. (2014b). N6- methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16, 191-198.
108. Wang, X., Zhao, B. S., Roundtree, I. A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H. and He, C. (2015). N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388-1399.
109. Xiao, W., Adhikari, S., Dahal, U., Chen, Y.-S., Hao, Y.-J., Sun, B.-F., Sun, H.-Y., Li, A., Ping, X.-L., Lai, W.-Y. et al. (2016). Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol. Cell 61, 507-519.
110. Yarham, J. W., Lamichhane, T. N., Pyle, A., Mattijssen, S., Baruffini, E., Bruni, F., Donnini, C., Vassilev, A., He, L., Blakely, E. L. et al. (2014). Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA. PLoS Genet. 6, e1004424.
111. Yu, A. T., Ge, J. and Yu, Y.-T. (2011). Pseudouridines in spliceosomal snRNAs. Protein Cell 2, 712-725.
112. Yue, Y., Liu, J. and He, C. (2015). RNA N6-methyladenosine methylation in posttranscriptional gene expression regulation. Genes Dev. 29, 1343-1355.
113. Zheng, G., Dahl, J. A., Niu, Y., Fedorcsak, P., Huang, C.-M., Li, C. J., Vagbo, C. B., Shi, Y., Wang, W.-L., Song, S.-H. et al. (2013). ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49, 18-29.
114. Zhou, J., Wan, J., Gao, X., Zhang, X., Jaffrey, S. R. and Qian, S.-B. (2015). Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature 526, 591-594.