Nucleoside modifications in the regulation of gene expression: focus on tRNA

Cellular and Molecular Life Sciences

Volumn 73, Issue 16, 2016, Pages 3075-3095

  Duechler, Markus ^a   Leszczyńska, Grażyna ^b   Sochacka, Elzbieta ^b   Nawrot, Barbara ^a  

^a CENTRE OF MOLECULAR AND MACROMOLECULAR STUDIES   (Poland)

^b LODZ UNIVERSITY OF TECHNOLOGY   (Poland)

Author keywords

Modified nucleosides; Regulation of gene expression; Stress signaling; Translation rate; tRNA

Indexed keywords

2 THIOURIDINE; MESSENGER RNA; METHYLTRANSFERASE; MITOCHONDRIAL RNA; NUCLEOSIDE; SULFUR; THIOURIDINE; TRANSFER RNA; UNCLASSIFIED DRUG; UNTRANSLATED RNA; URIDINE; ANTICODON; CODON;

ANTICODON; BASE PAIRING; CELL FUNCTION; CHEMICAL MODIFICATION; CODON USAGE; DELAYED TRANSLATION; DYNAMICS; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE INTERACTION; GENETIC DISORDER; HUMAN; MODIFICATION DYNAMICS; NONHUMAN; OXIDATIVE STRESS; PROTEIN SYNTHESIS REGULATION; REVIEW; RNA CLEAVAGE; ANIMAL; CHEMISTRY; CODON; CONFORMATION; GENETIC CODE; GENETICS; METABOLISM; MOLECULAR MODEL; PHYSIOLOGICAL STRESS; PROTEIN SYNTHESIS;

ANIMALS; ANTICODON; BASE PAIRING; CODON; GENE EXPRESSION REGULATION; GENETIC CODE; HUMANS; MODELS, MOLECULAR; NUCLEIC ACID CONFORMATION; NUCLEOSIDES; PROTEIN BIOSYNTHESIS; RNA, TRANSFER; STRESS, PHYSIOLOGICAL;

EID: 84964324457     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-016-2217-y     Document Type: Review

References (226)

1. Palstra RJ, Grosveld F (2012) Transcription factor binding at enhancers: shaping a genomic regulatory landscape in flux. Front Genet 3:195
2. Mili S, Shu HJ, Zhao Y, Piñol-Roma S (2001) Distinct RNP complexes of shuttling hnRNP proteins with pre-mRNA and mRNA: candidate intermediates in formation and export of mRNA. Mol Cell Biol 21:7307–7319
3. Nagai K, Muto Y, Pomeranz Krummel DA, Kambach C, Ignjatovic T, Walke S, Kuglstatter A (2001) Structure and assembly of the spliceosomal snRNPs. Novartis Medal Lecture. Biochem Soc Trans 29:15–26
4. Jia J, Yao P, Arif A, Fox PL (2013) Regulation and dysregulation of 3′UTR-mediated translational control. Curr Opin Genet Dev 23:29–34
5. Meyer KD, Jaffrey SR (2014) The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol 15:313–326
6. Yuan S, Tang H, Xing J, Fan X, Cai X, Li Q, Han P, Luo Y, Zhang Z, Jiang B, Dou Y, Gorospe M, Wang W (2014) Methylation by NSun2 represses the levels and function of microRNA 125b. Mol Cell Biol 34:3630–3641
7. Pichon X, Wilson LA, Stoneley M, Bastide A, King HA, Somers J, Willis AE (2012) RNA binding protein/RNA element interactions and the control of translation. Curr Protein Pept Sci 13:294–304
8. Grewal SS (2015) Why should cancer biologists care about tRNAs? tRNA synthesis, mRNA translation and the control of growth. Biochim Biophys Acta 1849:898–907
9. Björk GR, Hagervall TG (2014) Transfer RNA modification: presence, synthesis, and function. EcoSal Plus 6:1–68
10. Banerjee R, Chen S, Dare K, Gilreath M, Praetorius-Ibba M, Raina M, Reynolds NM, Rogers T, Roy H, Yadavalli SS, Ibba M (2010) tRNAs: cellular barcodes for amino acids. FEBS Lett 584:387–395
11. Nawrot B, Sochacka E, Düchler M (2011) tRNA structural and functional changes induced by oxidative stress. Cell Mol Life Sci 68:4023–4403
12. Lee YS, Shibata Y, Malhotra A, Dutta A (2009) A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 23:2639–2649
13. Shigematsu M, Kirino Y (2015) tRNA-derived short non-coding RNA as interacting partners of argonaute proteins. Gene Regul Syst Bio 9:27–33
14. Maute RL, Schneider C, Sumazin P, Holmes A, Califano A, Basso K, Dalla-Favera R (2013) tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci USA 110:1404–1409
15. Martens-Uzunova ES, Olvedy M, Jenster G (2013) Beyond microRNA–novel RNAs derived from small non-coding RNA and their implication in cancer. Cancer Lett 340:201–211
16. Yeung ML, Bennasser Y, Watashi K, Le SY, Houzet L, Jeang KT (2009) Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: evidence for the processing of a viral-cellular double-stranded RNA hybrid. Nucleic Acids Res 37:6575–6586
17. Machnicka MA, Milanowska K, Osman Oglou O, Purta E, Kurkowska M, Olchowik A, Januszewski W, Kalinowski S, Dunin-Horkawicz S, Rother KM, Helm M, Bujnicki JM, Grosjean H (2013) MODOMICS: a database of RNA modification pathways—2013 update. Nucleic Acids Res 41:D262–D267
18. Cantara WA, Crain PF, Rozenski J, McCloskey JA, Harris KA, Zhang X, Vendeix FA, Fabris D, Agris PF (2011) The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Res 39:D195–D201
19. Madore E, Florentz C, Giegé R, Sekine S, Yokoyama S, Lapointe J (1999) Effect of modified nucleotides on Escherichia coli tRNAGlu structure and on its aminoacylation by glutamyl-tRNA synthetase. Predominant and distinct roles of the mnm5 and s2 modifications of U34. Eur J Biochem 266:1128–1135
20. Klassen R, Paluszynski JP, Wemhoff S, Pfeiffer A, Fricke J, Meinhardt F (2008) The primary target of the killer toxin from Pichia acaciae is tRNA(Gln). Mol Microbiol 69:681–697
21. Saikia M, Krokowski D, Guan BJ, Ivanov P, Parisien M, Hu GF, Anderson P, Pan T, Hatzoglou M (2012) Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress. J Biol Chem 287:42708–42725
22. Schaefer M, Pollex T, Hanna K, Tuorto F, Meusburger M, Helm M, Lyko F (2010) RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev 24:1590–1595
23. Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, Humphreys P, Lukk M, Lombard P, Treps L, Popis M, Kellner S, Hölter SM, Garrett L, Wurst W, Becker L, Klopstock T, Fuchs H, Gailus-Durner V, Hrabĕ de Angelis M, Káradóttir RT, Helm M, Ule J, Gleeson JG, Odom DT, Frye M (2014) Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J 33:2020–2039
24. Manickam N, Joshi K, Bhatt MJ, Farabaugh PJ (2016) Effects of tRNA modification on translational accuracy depend on intrinsic codon–anticodon strength. Nucleic Acids Res 44:1871–1881
25. Hori H (2014) Methylated nucleosides in tRNA and tRNA methyltransferases. Front Genet 5:144
26. Zhou M, Guo J, Cha J, Chae M, Chen S, Barral JM, Sachs MS, Liu Y (2013) Non-optimal codon usage affects expression, structure and function of clock protein FRQ. Nature 495:111–115
27. Mami I, Pallet N (2015) Transfer RNA fragmentation and protein translation dynamics in the course of kidney injury. RNA Biol doi:10.1080/15476286.2015.1107704
28. Fu H, Feng J, Liu Q, Sun F, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2009) Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett 583:437–442
29. Yamasaki S, Ivanov P, Hu GF, Anderson P (2009) Angiogenin cleaves tRNA and promotes stress-induced translational repression. J Cell Biol 185:35–42
30. Czech A, Wende S, Mörl M, Pan T, Ignatova Z (2013) Reversible and rapid transfer-RNA deactivation as a mechanism of translational repression in stress. PLoS Genet 9:e1003767
31. Emara MM, Ivanov P, Hickman T, Dawra N, Tisdale S, Kedersha N, Hu GF, Anderson P (2010) Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly. J Biol Chem 285:10959–10968
32. Pizzo E, Sarcinelli C, Sheng J, Fusco S, Formiggini F, Netti P, Yu W, D’Alessio G, Hu GF (2013) Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and survival. J Cell Sci 126:4308–4319
33. Buchan JR (2013) Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153:1461–1474
34. Tomita K, Ogawa T, Uozumi T, Watanabe K, Masaki H (2000) A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine tRNAs at their anticodon loops. Proc Natl Acad Sci USA 97:8278–8283
35. Meineke B, Schwer B, Schaffrath R, Shuman S (2011) Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC. Nucleic Acids Res 39:687–700
36. Shigematsu M, Ogawa T, Kitamoto HK, Hidaka M, Masaki H (2012) Specific phase arrest of cell cycle restores cell viability against tRNA cleavage by killer toxin. Biochem Biophys Res Commun 420:750–754
37. Saxena SK, Sirdeshmukh R, Ardelt W, Mikulski SM, Shogen K, Youle RJ (2002) Entry into cells and selective degradation of tRNAs by a cytotoxic member of the RNase A family. J Biol Chem 277:15142–15146
38. Meineke B, Kast A, Schwer B, Meinhardt F, Shuman S, Klassen R (2012) A fungal anticodon nuclease ribotoxin exploits a secondary cleavage site to evade tRNA repair. RNA 18:1716–1724
39. Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S, Kellner S, Frye M, Helm M, Stoecklin G, Lyko F (2012) RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol 19:900–905
40. Mishima E, Inoue C, Saigusa D, Inoue R, Ito K, Suzuki Y et al (2014) Conformational change in transfer RNA is an early indicator of acute cellular damage. J Am Soc Nephrol 25:2316–2326
41. Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P (2011) Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 43:613–623
42. Dhahbi JM, Spindler SR, Atamna H, Yamakawa A, Boffelli D, Mote P, Martin DI (2013) 5′ tRNA halves are present as abundant complexes in serum, concentrated in blood cells, and modulated by aging and calorie restriction. BMC Genom 14:298
43. Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L, Tavazoie SF (2015) Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell 161:790–802
44. Casas E, Cai G, Neill JD (2015) Characterization of circulating transfer RNA-derived RNA fragments in cattle. Front Genet 6:271
45. Telonis AG, Loher P, Honda S, Jing Y, Palazzo J, Kirino Y, Rigoutsos I (2015) Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget 6:24797–24822
46. Mei Y, Yong J, Liu H, Shi Y, Meinkoth J, Dreyfuss G, Yang X (2010) tRNA binds to cytochrome c and inhibits caspase activation. Mol Cell 37:668–678
47. Saikia M, Jobava R, Parisien M, Putnam A, Krokowski D, Gao XH, Guan BJ, Yuan Y, Jankowsky E, Feng Z, Hu GF, Pusztai-Carey M, Gorla M, Sepuri NB, Pan T, Hatzoglou M (2014) Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol Cell Biol 34:2450–2463
48. Li Q, Hu B, Hu GW, Chen CY, Niu X, Liu J, Zhou SM, Zhang CQ, Wang Y, Deng ZF (2016) tRNA-derived small non-coding RNAs in response to ischemia inhibit angiogenesis. Sci Rep 6:20850
49. Honda S, Loher P, Shigematsu M, Palazzo JP, Suzuki R, Imoto I, Rigoutsos I, Kirino Y (2015) Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc Natl Acad Sci USA 112:E3816–E3825
50. Lopes RR, Kessler AC, Polycarpo C, Alfonzo JD (2015) Cutting, dicing, healing and sealing: the molecular surgery of tRNA. Wiley Interdiscip Rev RNA 6:337–349
51. Kanai A (2015) Disrupted tRNA genes and tRNA fragments: a perspective on tRNA gene evolution. Life (Basel) 5:321–331
52. Torres AG, Batlle E, Ribas de Pouplana L (2014) Role of tRNA modifications in human diseases. Trends Mol Med 20:306–314
53. Guy MP, Shaw M, Weiner CL, Hobson L, Stark Z, Rose K, Kalscheuer VM, Gecz J, Phizicky EM (2015) Defects in tRNA anticodon loop 2′-O-methylation are implicated in nonsyndromic X-linked intellectual disability due to mutations in FTSJ1. Hum Mutat 36:1176–1187
54. Guy MP, Phizicky EM (2015) Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes. RNA 21:61–74
55. Karlsborn T, Tükenmez H, Chen C, Byström AS (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
56. Thiaville PC, de Crecy-Lagard V (2015) The emerging role of complex modifications of tRNALysUUU in signaling pathways. Microb Cell 2:1–4
57. Wilusz JE (2015) Controlling translation via modulation of tRNA levels. Wiley Interdiscip Rev RNA 6:453–470
58. Agris PF, Vendeix FA, Graham WD (2007) tRNA’s wobble decoding of the genome: 40 years of modification. J Mol Biol 366:1–13
59. Krisko A, Copic T, Gabaldón T, Lehner B, Supek F (2014) Inferring gene function from evolutionary change in signatures of translation efficiency. Genome Biol 15:R44
60. Begley U, Dyavaiah M, Patil A, Rooney JP, Direnzo D et al (2007) Trm9-catalyzed tRNA modifications link translation to the DNA damage response. Mol Cell 28:860–870
61. Brandmayr C, Wagner M, Brückl T, Globisch D, Pearson D, Kneuttinger AC, Reiter V, Hienzsch A, Koch S, Thoma I, Thumbs P, Michalakis S, Müller M, Biel M, Carell T (2012) Isotope-based analysis of modified tRNA nucleosides correlates modification density with translational efficiency. Angew Chem Int Ed Engl 51:11162–11165
62. Rezgui VA, Tyagi K, Ranjan N, Konevega AL, Mittelstaet J, Rodnina MV, Peter M, Pedrioli PG (2013) tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding. Proc Natl Acad Sci USA 110:12289–12294
63. Tükenmez H, Xu H, Esberg A, Byström AS (2015) The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes. Nucleic Acids Res 43:9489–9499
64. Lamichhane TN, Blewett NH, Crawford AK, Cherkasova VA, Iben JR, Begley TJ, Farabaugh PJ, Maraia RJ (2013) Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies in fission yeast. Mol Cell Biol 33:2918–2929
65. Miyauchi K, Kimura S, Suzuki T (2013) A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification. Nat Chem Biol 9:105–111
66. Matuszewski M, Sochacka E (2014) Stability studies on the newly discovered cyclic form of tRNA N(6)-threonylcarbamoyladenosine (ct(6)A). Bioorg Med Chem Lett 24:2703–2706
67. Crick FHC (1966) Codon–anticodon pairing: the wobble hypothesis. J Mol Biol 19:548–555
68. Sylvers LA, Rogers KC, Shimizu M, Ohtsuka E, Söll D (1993) A 2-thiouridine derivative in tRNAGlu is a positive determinant for aminoacylation by Escherichia coli glutamyl-tRNA synthetase. Biochemistry 32:3836–3841
69. Karikó K, Buckstein M, Ni H, Weissman D (2005) Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23:165–175
70. Nallagatla SR, Bevilacqua PC (2008) Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner. RNA 14:1201–1213
71. Nallagatla SR, Jones CN, Ghosh SK, Sharma SD, Cameron CE, Spremulli LL, Bevilacqua PC (2013) Native tertiary structure and nucleoside modifications suppress tRNA’s intrinsic ability to activate the innate immune sensor PKR. PLoS One 8:e57905
72. Isel C, Marquet R, Keith G, Ehresmann C, Ehresmann B (1993) Modified nucleotides of tRNA(3Lys) modulate primer/template loop-loop interaction in the initiation complex of HIV-1 reverse transcription. J Biol Chem 268:25269–25272
73. Watanabe K, Oshima T, Saneyoshi M, Nishimura S (1974) Replacement of ribothymidine by 5-methyl-2-thiouridine in sequence GT psi C in tRNA of an extreme thermophile. FEBS Lett 43:59–63
74. Sprinzl M, Horn C, Brown M, Ioudovitch A, Steinberg S (1998) Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res 26:148–153
75. Kowalak JA, Dalluge JJ, McCloskey JA, Stetter KO (1994) The role of posttranscriptional modification in stabilization of transfer RNA from hyperthermophiles. Biochemistry 33:7869–7876
76. Laxman S, Sutter BM, Wu X, Kumar S, Guo X, Trudgian DC, Mirzaei H, Tu BP (2013) Sulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation. Cell 154:416–429
77. Han L, Kon Y, Phizicky EM (2015) Functional importance of Ψ38 and Ψ39 in distinct tRNAs, amplified for tRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification in yeast. RNA 21:188–201
78. Yarian C, Townsend H, Czestkowski W, Sochacka E, Malkiewicz AJ, Guenther R, Miskiewicz A, Agris PF (2002) Accurate translation of the genetic code depends on tRNA modified nucleosides. J Biol Chem 277:16391–16395
79. Sochacka E, Kraszewska K, Sochacki M, Sobczak M, Janicka M, Nawrot B (2011) The 2-thiouridine unit in the RNA strand is desulfured predominantly to 4-pyrimidinone nucleoside under in vitro oxidative stress conditions. Chem Commun (Camb) 47:4914–4916
80. Sochacka E, Bartos P, Kraszewska K, Nawrot B (2013) Desulfuration of 2-thiouridine with hydrogen peroxide in the physiological pH range 6.6-7.6 is pH-dependent and results in two distinct products. Bioorg Med Chem Lett 23:5803–5805
81. Bartos P, Ebenryter-Olbinska K, Sochacka E, Nawrot B (2015) The influence of the C5 substituent on the 2-thiouridine desulfuration pathway and the conformational analysis of the resulting 4-pyrimidinone products. Bioorg Med Chem 23:5587–5594
82. Sochacka E, Szczepanowski RH, Cypryk M, Sobczak M, Janicka M, Kraszewska K, Bartos P, Chwialkowska A, Nawrot B (2015) 2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes. Nucleic Acids Res 43:2499–2512
83. Srinivasan T, Kumaran K, Selvakumar R, Velmurugan D, Sudarsanam D (2013) Exploring GpG bases next to anticodon in tRNA subsets. Bioinformation 9:466–470
84. Tuorto F, Herbst F, Alerasool N, Bender S, Popp O, Federico G, Reitter S, Liebers R, Stoecklin G, Gröne HJ, Dittmar G, Glimm H, Lyko F (2015) The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J 34:2350–2362
85. Björk GR, Huang B, Persson OP, Byström AS (2007) A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast. RNA 13:1245–1255
86. D’Silva S, Haider SJ, Phizicky EM (2011) A domain of the actin binding protein Abp140 is the yeast methyltransferase responsible for 3-methylcytidine modification in the tRNA anticodon loop. RNA 17:1100–1110
87. Haag S, Warda AS, Kretschmer J, Günnigmann MA, Höbartner C, Bohnsack MT (2015) NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. RNA 21:1532–1543
88. Pietromonaco S, Denslow N, O‘Brien TW (1991) Proteins of mammalian mitochondrial ribosomes. Biochimie 73:827–836
89. Christian BE, Spremulli LL (2012) Mechanism of protein biosynthesis in mammalian mitochondria. Biochim Biophys Acta 1819:1035–1054
90. Boczonadi V, Horvath R (2014) Mitochondria: impaired mitochondrial translation in human disease. Int J Biochem Cell Biol 48:77–84
91. Salinas-Giegé T, Giegé P (2015) tRNA biology in mitochondria. Int J Mol Sci 16:4518–4559
92. Powell ChA, Nicholls TJ, Minczuk M (2015) Nuclear-encoded factors involved in post-transcriptional processing and modification of mitochondrial tRNAs in human disease Front Gen 6:1–14
93. Suzuki T, Nagao A, Suzuki T (2011) Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases. Annu Rev Genet 45:299–329
94. Watanabe K, Yokobori S (2011) tRNA modification and genetic code variations in animal mitochondria. J Nucleic Acids 2011:623095
95. Suzuki T, Suzuki T (2014) A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs. Nucleic Acids Res 42:7346–7357
96. Machnicka MA, Olchowik A, Grosjean H, Bujnicki JM (2014) Distribution and frequencies of post-transcriptional modifications in tRNAs. RNA Biol 11:1619–1629
97. Helm M, Brulé H, Degoul F, Cepanec C, Leroux J-P, Giegé R, Florentz C (1998) The presence of modified nucleotides is required for cloverleaf folding of a human mitochondrial tRNA. Nucleic Acids Res 26:1636–1643
98. Jones CI, Spencer AC, Hsu JL, Spremulli LL, Martinis SA, DeRider M, Agris PF (2006) A Counterintuitive Mg2+-dependent and modification-assisted functional folding of mitochondrial tRNAs. J Mol Biol 362:771–786
99. Bhaskaran H, Taniguchi T, Suzuki T, Suzuki T, Perona JJ (2014) Structural dynamics of a mitochondrial tRNA possessing weak thermodynamic stability. Biochemistry 53:1456–1465
100. Helm M, Giege R, Florentz C (1999) A Watson–Crick base-pair-disrupting methyl group (m1A9) is sufficient for cloverleaf folding of human mitochondrial tRNALys. Biochemistry 38:13338–13346
101. Voigts-Hoffmann F, Hengesbach M, Kobitski AY, van Aerschot A, Herdewijn P, Nienhaus GU, Helm M (2007) A methyl group controls conformational equilibrium in human mitochondrial tRNALys. J Am Chem Soc 129:13382–13383
102. Moraes CT, Ciacci F, Bonilla E, Ionasescu V, Schon EA, Dimauro S (1993) A mitochondrial transfer-RNA anticodon swap associated with a muscle disease. Nat Genet 4:284–288
103. Enriquez JA, Chomyn A, Attardi G (1995) mtDNA mutation in MERRF-syndrome causes defective aminoacylation of tRNALys and premature translation termination. Nat Genet 10:47–55
104. Armengod NE, Meseguer S, Villarroya M, Prado S, Moukadiri I, Ruiz-Partida R, Garzon MJ, Navarro-Gonzalez C, Matinez-Zamora A (2014) Modification of the wobble uridine in bacterial and mitochondrial tRNAs reading NNA/NNG triplets of 2-codon boxes. RNA Biol 11:1495–1507
105. Yasukawa T, Suzuki T, Ishii N, Ueda T, Ohta S, Watanabe K (2000) Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNALys with the MERRF encephalomyopathy pathogenic mutation. FEBS Lett 467:175–178
106. Suzuki T, Suzuki T, Wada T, Saigo K, Watanabe K (2001) Novel taurine-containing derivatives and mitochondrial human diseases. Nucleic Acids Res Supp. No.1:257–258
107. Moriya J, Yokogawa T, Wakita K, Ueda T, Nishikawa K, Crain PF, Hashizume T, Pomerantz SC, McCloskey JA, Kawai G et al (1994) A novel modified nucleoside found at the first position of the anticodon of methionine tRNA from bovine liver mitochondria. Biochemistry 33:2234–2239
108. Suzuki T, Nagao A, Suzuki T (2011) Human mitochondrial diseases caused by lack of taurine modification in mitochondrial tRNAs. Wiley Interdiscip Rev RNA 2:376–386
109. Levinger L, Morl M, Florentz C (2004) Mitochondrial tRNA 3′ end metabolism and human disease. Nucleic Acids Res 32:5430–5441
110. Belostotsky R, Frishberg Y, Entelis N (2012) Human mitochondrial tRNA quality control in health and disease: a channelling mechanism? RNA Biol 9:33–39
111. Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC (1990) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 61:931–937
112. Lightowlers RN, Taylor RW, Turnbull DM (2015) Mutations causing mitochondrial disease: what is new challenges remain? Science 349:1494–1499
113. Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653
114. Goto Y, Nonaka I, Horai S (1991) A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Biochim Biophys Acta 1097:238–240
115. Yasukawa T, Suzuki T, Suzuki T, Ueda T, Ohta S, Watanabe K (2000) Modification defect at anticodon wobble nucleotide of mitochondrial tRNAsLeu(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. J Biol Chem 275:4251–4257
116. Kirino Y, Goto Y, Campos Y, Arenas J, Suzuki T (2005) Specific correlation between the wobble modification deficiency in mutant tRNAs and the clinical features of a human mitochondrial disease. Proc Natl Acad Sci USA 102:7127–7132
117. Yasukawa T, Kirino Y, Ishii N, Holt IJ, Jacobs HT, Makifuchi T, Fukuhara N, Ohta S, Suzuki T, Watanabe K (2005) Wobble modification deficiency in mutant tRNAs in patients with mitochondrial diseases. FEBS Lett 579:2948–2952
118. Kurata S, Weixlbaumer A, Ohtsuki T, Shimazaki T, Wada T, Kirino Y, Takai K, Watanabe K, Ramakrishnan V, Suzuki T (2008) Modified uridines with C5-methylene substituents at the first position of the tRNA anticodon stabilize U•G wobble pairing during decoding. J Biol Chem 283:18801–18811
119. Rodriguez-Hernandez A, Spears JL, Gaston KW, Limbach PA, Gamper H, Hou YM, Kaiser R, Agris PF, Perona JJ (2013) Structural and mechanistic basis for enhanced translational efficiency by 2-thiouridine at the tRNA anticodon wobble position. J Mol Biol 425:3888–3906
120. Ashraf SS, Sochacka E, Cain R, Guenther R, Malkiewicz A, Agris PF (1999) Single atom modification (O → S) of tRNA confers ribosome binding. RNA 5:188–194
121. Yasukawa T, Suzuki T, Ishii N, Ohta S, Watanabe K (2001) Wobble modification defect in tRNA disturbs codon–anticodon interaction in a mitochondrial disease. EMBO J 20:4794–4802
122. Wang X, Yan Q, Guan MX (2010) Combination of the loss of cmnm5U34 with the lack of s2U34 modifications of tRNALys, tRNAGlu, and tRNAGln altered mitochondrial biogenesis and respiration. J Mol Biol 395:1038–1048
123. Schara U, von Kleist-Retzow JC, Lainka E, Gerner P, Pyle A, Smith PM, Lochmuller H, Czermin B, Abicht A, Holinski-Feder E, Horvath R (2011) Acute liver failure with subsequent cirrhosis as the primary manifestation of TRMU mutations. J Inherit Metab Dis 34:197–201
124. Ghezzi D, Baruffini E, Haack TB, Invernizzi F, Melchionda L, Dallabona C, Strom TM, Parini R, Burlina AB, Meitinger T, Prokisch H, Ferrero I, Zeviani M (2012) Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis. Am J Hum Genet 90:1079–1087
125. Tischner Ch, Hofer A, Wulff V, Stepek J, Dumitru I, Becker L, Haak T, Kremer L, Datta AN, Sperl W, Floss T, Wurst W, Chrzanowska-Lightowlers Z, Hrabe de Angelis M, Klopstock T, Prokisch H, Wenz T (2015) MTO1 mediates tissue-specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention. Hum Mol Genet 24:2247–2266
126. Sasarman F, Antonicka H, Horvath R, Shoubridge EA (2011) The 2-thiouridylase function of the human MTU1 (TRMU) enzyme is dispensable for mitochondrial translation. Hum Mol Genet 20:4634–4643
127. Boczonadi V, Smith PM, Pyle A, Gomez-Duran A, Schara U, Tulinus M, Chinnery PF, Horvath R (2013) Altered 2-thiouridylation impairs mitochondrial translation in reversible infantile respiratory chain deficiency. Hum Mol Genet 22:4602–4615
128. Takemoto C, Spremulli LL, Benkowski LA, Ueda T, Yokogawa T, Watanabe K (2009) Unconventional decoding of the AUA codon as methionine by mitochondrial tRNAMet with the anticodon f5CAU as revealed with a mitochondrial in vitro translation system. Nucleic Acids Res 37:1616–1627
129. BilbilleY Gustilo EM, Harris KA, Jones CN, Lusic H, Kaiser RJ, Delaney MO, Spremulli LL, Deiters A, Agris PF (2011) The human mitochondrial tRNAMet: structure/function relationship of a unique modification in the decoding of unconventional codons. J Mol Biol 406:257–274
130. Cantara WA, Murphy FV, Demirci H, Agris PF (2013) Expanded use of sense codons is regulated by modified cytidines in tRNA. Proc Natl Acad Sci USA 110:10964–10969
131. Yokoyama S, Miyazawa T, Iitaka Y, Yamaizumi Z, Kasai H, Nishimura S (1979) Three-dimensional structure of hypermodified nucleoside Q located in the wobbling position of tRNA. Nature 282:107–109
132. Morris RC, Brown KG, Elliott MS (1999) The effect of queuosine on tRNA structure and function. J Biomol Struct Dyn 16:757–774
133. Vinayak M, Pathak C (2010) Queuosine modification of tRNA: its divergent role in cellular machinery. Biosci Rep 30:135–148
134. Meier F, Suter B, Grosjean H, Keith G, Kubli E (1985) Queuosine modification of the wobble base in tRNAHis influences ‘in vivo’ decoding properties. EMBO J 4:823–827
135. Murphy FV IV, Ramakrishnan V, Malkiewicz A, Agris PF (2004) The role of modification in codon discrimination by tRNALysUUU. Nat Struct Mol Biol 11:1186–1191
136. Thiaville PC, El Yacoubi B, Köhrer C, Thiaville JJ, Deutsch C, Iwata-Reuyl D, Bacusmo JM, Armengaud J, Bessho Y, Wetzel C, Cao X, Limbach PA, RajBhandary UL, de Crécy-Lagard V (2015) Essentiality of threonylcarbamoyladenosine (t(6) A), a universal tRNA modification, in bacteria. Mol Microbiol 98:1199–1221
137. Wan LCK, Mao DYL, Neculai D, Strecker J, Chiovitti D, Kurinov I, Poda G, Thevakumaran N, Yuan F, Szilard RK, Lissina E, Nislow C, Caudy AA, Durocher D, Sicheri F (2013) Reconstitution and characterization of eukaryotic N6-threonylcarbamoylation of tRNA using a minimal enzyme system. Nucleic Acids Res 41:6332–6346
138. Urbonavicius J, Qian Q, Durand JM, Hagervall TG, Bjork GR (2001) Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J 20:4863–4873
139. El Yacoubi B, Bailly M, de Crecy-Lagard V (2012) Biosynthesis and function of posttranscriptional modifications of transfer RNAs. Annu Rev Genet 46:69–95
140. Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E, Bruni F, Donnini C, Vassilev A, He L, Blakely EL, Griffin H, Santibanez-Koref M, Bindoff LA, Ferrero I, Chinnery PF, McFarland R, Maraia RJ, Taylor RW (2014) Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA. PLoS Genet 10:e1004424
141. Reiter V, Matschkal DMS, Wagner M, Globisch D, Kneuttinger AC, Müller M, Carell T (2012) The CDK5 repressor CDK5RAP1 is a methylthiotransferase acting on nuclear and mitochondrial RNA. Nucleic Acids Res 40:6235–6240
142. Wei FY, Zhou B, Suzuki T, Miyata K, Ujihara Y, Horiguchi H, Takahashi N, Xie P, Michiue H, Fujimura A, Kaitsuka T, Matsui H, Koga Y, Mohri S, Suzuki T, Oike Y, Tomizawa K (2015) Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans. Cell Metab 21:428–442
143. Davis DR (1995) Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res 23:5020–5026
144. Newby MI, Greenbaum NL (2002) Investigation of overhauser effects between pseudouridine and water protons in RNA helices. Proc Natl Acad Sci USA 99:12697–12702
145. Charette M, Gray MW (2000) Pseudouridine in RNA: what, where, how, and why. IUBMB Life 49:341–351
146. Hamma T, Ferré-D’Amaré AR (2006) Pseudouridine synthases. Chem Biol 13:1125–1135
147. Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel-Ghodsian N (2004) Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am J Hum Genet 74:1303–1308
148. Fernandez-Vizarra E, Berardinelli A, Valente L, Tiranti V, Zeviani M (2007) Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anemia (MLASA). J Med Genet 44:173–180
149. Endres L, Dedon PC, Begley TJ (2015) Codon-biased translation can be regulated by wobble-base tRNA modification systems during cellular stress responses. RNA Biol 12:603–614
150. Chan CT, Deng W, Li F, DeMott MS, Babu IR, Begley TJ, Dedon PC (2015) Highly predictive reprogramming of tRNA modifications is linked to selective expression of codon-biased genes. Chem Res Toxicol 28:978–988
151. Chan CTY, Dyavaiah M, DeMott MS, Taghizadeh K, Dedon PC et al (2010) A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. PLoS Genet 6:e1001247
152. Chan CT, Pang YL, Deng W, Babu IR, Dyavaiah M, Begley TJ, Dedon PC (2012) Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins. Nat Commun 3:937
153. Preston MA, D’Silva S, Kon Y, Phizicky EM (2013) tRNAHis 5-methylcytidine levels increase in response to several growth arrest conditions in Saccharomyces cerevisiae. RNA 19:243–256
154. Endres L, Begley U, Clark R, Gu C, Dziergowska A, Małkiewicz A, Melendez JA, Dedon PC, Begley TJ (2015) Alkbh8 regulates selenocysteine-protein expression to protect against reactive oxygen species damage. PLoS One 10:e0131335
155. Fernandez-Vazquez J, Vargas-Perez I, Sanso M, Buhne K, Carmona M et al (2013) Modification of tRNALys UUU by elongator is essential for efficient translation of stress mRNAs. PLoS Genet 9:e1003647
156. Damon JR, Pincus D, Ploegh HL (2015) tRNA thiolation links translation to stress responses in Saccharomyces cerevisiae. Mol Biol Cell 26:270–282
157. Vendeix FA, Murphy FV 4th, Cantara WA, Leszczyńska G, Gustilo EM, Sproat B, Malkiewicz A, Agris PF (2012) Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism. J Mol Biol 416:467–485
158. Sierzputowska-Gracz H, Sochacka E, Malkiewicz A, Kuo K, Gehrke CW, Agris PF (1987) Chemistry and structure of modified uridines in the anticodon, wobble position of transfer RNA are determined by thiolation. J Am Chem Soc 109:7171–7177
159. Agris PF, Sierzputowska-Gracz H, Smith W, Malkiewicz A, Sochacka E, Nawrot B (1992) Thiolation of uridine carbon-2 restricts the motional dynamics of the transfer RNA wobble position nucleoside. J Am Chem Soc 114:2652–2656
160. Yamamoto Y, Yokoyama S, Miyazawa T, Watanabe K, Higuchi S (1983) NMR analyses on the molecular mechanism of the conformational rigidity of 2-thioribothymidine, a modified nucleoside in extreme thermophile tRNAs. FEBS Lett 157:95–99
161. Sundaram M, Durant PC, Davis DR (2000) Hypermodified nucleosides in the anticodon of tRNALys stabilize a canonical U-turn structure. Biochemistry 39:12575–12584
162. Testa SM, Disney MD, Turner DH, Kierzek R (1999) Thermodynamics of RNA-RNA duplexes with 2- or 4-thiouridines: implications for antisense design and targeting a group I intron. Biochemistry 38:16655–16662
163. Kumar RK, Davis DR (1997) Synthesis and studies on the effect of 2-thiouridine and 4-thiouridine on sugar conformation and RNA duplex stability. Nucleic Acids Res 25:1272–1280
164. Shohda K, Okamoto I, Wada T, Seio K, Sekine M (2000) Synthesis and properties of 2′-O-methyl-2-thiouridine and oligoribonucleotides containing 2′-O-methyl-2-thiouridine. Bioorg Med Chem Lett 10:1795–1798
165. Okamoto I, Seio K, Sekine M (2006) Incorporation of 2′-O-methyl-2-thiouridine into oligoribonucleotides induced stable A-form structure. Chem Lett 35:136–137
166. Larsen AT, Fahrenbach AC, Sheng J, Pian J, Szostak JW (2015) Thermodynamic insights into 2-thiouridine-enhanced RNA hybridization. Nucleic Acids Res 43:7675–7687
167. Donohue J (1969) On N–H–S hydrogen bonds. J Mol Biol 45:231–235
168. Krüger MK, Sørensen MA (1998) Aminoacylation of hypomodified tRNAGlu in vivo. J Mol Biol 284:609–620
169. Egert E, Lindner HJ, Hillen W, Boehm MC (1980) Influence of substituents at the 5 position on the structure of uridine. J Am Chem Soc 102:3707–3713
170. Patil A, Chan CT, Dyavaiah M, Rooney JP, Dedon PC, Begley TJ (2012) Translational infidelity-induced protein stress results from a deficiency in Trm9-catalyzed tRNA modifications. RNA Biol 9:990–1001
171. Klassen R, Grunewald P, Thüring KL, Eichler C, Helm M, Schaffrath R (2015) Loss of anticodon wobble uridine modifications affects tRNA(Lys) function and protein levels in Saccharomyces cerevisiae. PLoS One 10:e0119261
172. Patil A, Dyavaiah M, Joseph F, Rooney JP, Chan CT, Dedon PC, Begley TJ (2012) Increased tRNA modification and gene-specific codon usage regulate cell cycle progression during the DNA damage response. Cell Cycle 11:3656–3665
173. Bauer F, Matsuyama A, Candiracci J, Dieu M, Scheliga J, Wolf DA, Yoshida M, Hermand D (2012) Translational control of cell division by elongator. Cell Rep 1:424–433
174. Karlsborn T, Tükenmez H, Mahmud AK, Xu F, Xu H, Byström AS (2014) Elongator, a conserved complex required for wobble uridine modifications in eukaryotes. RNA Biol 11:1519–1528
175. Chen C, Huang B, Eliasson M, Rydén P, Byström AS (2011) Elongator complex influences telomeric gene silencing and DNA damage response by its role in wobble uridine tRNA modification. PLoS Genet 7:e1002258
176. Sakai Y, Miyauchi K, Kimura S, Suzuki T (2016) Biogenesis and growth phase-dependent alteration of 5-ethoxycarbonylmethoxyuridine in tRNA anticodons. Nucleic Acids Res 44:509–523
177. Takai K (2005) Possible conformations of 5-aminomethyluridine derivatives recognizing a G at the third position of the codon. Nucleic Acids Symp Ser 40:317–318
178. Rozov A, Demeshkina N, Khusainov I, Westhof E, Yusupov M, Yusupova G (2016) Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code. Nat Commun 7:10457
179. Dumelin CE (2012) Discovery and biological characterization of geranylated RNA in bacteria. Nat Chem Biol 8:913–919
180. Takai K, Yokoyama S (2003) Roles of 5-substituents of tRNA wobble uridines in the recognition of purine-ending codons. Nucleic Acids Res 31:6383–6391
181. Hussain S, Aleksic J, Blanco S, Dietmann S, Frye M (2013) Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome Biol 14:215
182. Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, Suter CM, Preiss T (2012) Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res 40:5023–5033
183. Carlile TM, Rojas-Duran MF, Zinshteyn B, Shin H, Bartoli KM, Gilbert WV (2014) Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515:143–146
184. Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, León-Ricardo BX, Engreitz JM, Guttman M, Satija R, Lander ES, Fink G, Regev A (2014) Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159:148–162
185. 6A RNA methylation. Nat Rev Genet 15:293–306
186. Lee M, Kim B, Kim VN (2014) Emerging roles of RNA modification: m(6)A and U-tail. Cell 158:980–987
187. Wang X, He C (2014) Dynamic RNA modifications in posttranscriptional regulation. Mol Cell 56:5–12
188. Delatte B, Wang F, Ngoc LV, Collignon E, Bonvin E, Deplus R, Calonne E, Hassabi B, Putmans P, Awe S, Wetzel C, Kreher J, Soin R, Creppe C, Limbach PA, Gueydan C, Kruys V, Brehm A, Minakhina S, Defrance M, Steward R, Fuks F (2016) RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science 351:282–285
189. Wei CM, Gershowitz A, Moss B (1976) 5′-terminal and internal methylated nucleotide sequences in Hela cell messenger RNA. Biochemistry 15:397–401
190. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, Cesarkas K, Jacob-Hirsch J, Amariglio N, Kupiec M, Sorek R, Rechavi G (2012) Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201–206
191. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–1646
192. Fustin JM, Doi M, Yamaguchi Y, Hida H, Nishimura S, Yoshida M, Isagawa T, Morioka MS, Kakeya H, Manabe I, Okamura H (2013) RNA methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155:793–806
193. Jia GF, Fu Y, Zhao X, Dai Q, Zheng GQ, Yang Y et al (2011) N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 7:885–887
194. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vågbø CB, Shi Y, Wang WL, Song SH, Lu Z, Bosmans RP, Dai Q, Hao YJ, Yang X, Zhao WM, Tong WM, Wang XJ, Bogdan F, Furu K, Fu Y, Jia G, Zhao X, Liu J, Krokan HE, Klungland A, Yang YG, He C (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 49:18–29
195. Liu JZ, Yue YN, Han DL, Wang X, Fu Y, Zhang L et al (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N-6-adenosine methylation. Nat Chem Biol 10:93–95
196. Liu J, Jia G (2014) Methylation modifications in eukaryotic messenger RNA. J Genet Genomics 41:21–33
197. Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, Ren B, Pan T, He C (2014) N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505:117–120
198. Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T (2015) N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518:560–564
199. Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB (2015) Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature 526:591–594
200. Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian SB, Jaffrey SR (2015) 5′ UTR m(6)A promotes cap-independent translation. Cell 163:999–1010
201. Roost C, Lynch SR, Batista PJ, Qu K, Chang HY, Kool ET (2015) Structure and thermodynamics of N6-methyladenosine in RNA: a spring-loaded base modification. J Am Chem Soc 137:2107–2115
202. Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H, He C (2015) N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 161:1388–1399
203. Batista PJ, Molinie B, Wang J, Qu K, Zhang J, Li L, Bouley DM, Lujan E, Haddad B, Daneshvar K, Carter AC, Flynn RA, Zhou C, Lim KS, Dedon P, Wernig M, Mullen AC, Xing Y, Giallourakis CC, Chang HY (2014) m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15:707–719
204. Geula S, Moshitch-Moshkovitz S, Dominissini D, Mansour AA, Kol N, Salmon-Divon M, Hershkovitz V, Peer E, Mor N, Manor YS, Ben-Haim MS, Eyal E, Yunger S, Pinto Y, Jaitin DA, Viukov S, Rais Y, Krupalnik V, Chomsky E, Zerbib M, Maza I, Rechavi Y, Massarwa R, Hanna S, Amit I, Levanon EY, Amariglio N, Stern-Ginossar N, Novershtern N, Rechavi G, Hanna JH (2015) Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347:1002–1006
205. Chen T, Hao YJ, Zhang Y, Li MM, Wang M, Han W, Wu Y, Lv Y, Hao J, Wang L, Li A, Yang Y, Jin KX, Zhao X, Li Y, Ping XL, Lai WY, Wu LG, Jiang G, Wang HL, Sang L, Wang XJ, Yang YG, Zhou Q (2015) m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 16:289–301
206. Choi J, Ieong KW, Demirci H, Chen J, Petrov A, Prabhakar A, O’Leary SE, Dominissini D, Rechavi G, Soltis SM, Ehrenberg M, Puglisi JD (2016) N(6)-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics. Nat Struct Mol Biol 23:110–115
207. Hudson BH, Zaher HS (2015) O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity. RNA 21:1648–1659
208. Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, Peer E, Kol N, Ben-Haim MS, Dai Q, Di Segni A, Salmon-Divon M, Clark WC, Zheng G, Pan T, Solomon O, Eyal E, Hershkovitz V, Han D, Doré LC, Amariglio N, Rechavi G, He C (2016) The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature 530:441–446
209. Lovejoy AF, Riordan DP, Brown PO (2014) Transcriptome-wide mapping of pseudouridines: pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLoS One 9:e110799
210. Zhao BS, He C (2015) Pseudouridine in a new era of RNA modifications. Cell Res 25:153–154
211. Karijolich J, Yu YT (2011) Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474:395–398
212. Roundtree IA, He C (2015) RNA epigenetics-chemical messages for posttranscriptional gene regulation. Curr Opin Chem Biol 30:46–51
213. Berulava T, Rahmann S, Rademacher K, Klein-Hitpass L, Horsthemke B (2015) N6-adenosine methylation in MiRNAs. PLoS One 10:e0118438
214. Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF (2015) N6-methyladenosine marks primary microRNAs for processing. Nature 519:482–485
215. Grosjean H, de Crécy-Lagard V, Marck C (2010) Deciphering synonymous codons in the three domains of life: co-evolution with specific tRNA modification enzymes. FEBS Lett 584:252–264
216. O’Brien EP, Ciryam P, Vendruscolo M, Dobson CM (2014) Understanding the influence of codon translation rates on co-translational protein folding. Acc Chem Res 47:1536–1544
217. O’Brien EP, Vendruscolo M, Dobson CM (2014) Kinetic modelling indicates that fast-translating codons can coordinate co-translational protein folding by avoiding misfolded intermediates. Nat Commun 5:2988
218. Yu CH, Dang Y, Zhou Z, Wu C, Zhao F, Sachs MS, Liu Y (2015) Codon usage influences the local rate of translation elongation to regulate estimated protein folding. Mol Cell 59:744–754
219. Dana A, Tuller T (2014) The effect of tRNA levels on decoding times of mRNA codons. Nucleic Acids Res 42:9171–9181
220. Nedialkova DD, Leidel SA (2015) Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell 161:1606–1618
221. Zinshteyn B, Gilbert WV (2013) Loss of a conserved tRNA anticodon modification perturbs cellular signaling. PLoS Genet 9:e1003675
222. Deng W, Babu R, Su D, Yin S, Begley TJ, Dedon PC (2015) Trm9-catalyzed tRNA modifications regulate global protein expression by codon-biased translation. PLoS Genet 11:e1005706
223. Tuller T, Carmi A, Vestsigian K, Navon S, Dorfan Y, Zaborske J, Pan T, Dahan O, Furman I, Pilpel Y (2010) An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell 141:344–354
224. López D, Pazos F (2015) Protein functional features are reflected in the patterns of mRNA translation speed. BMC Genom 16:513
225. Zhou M, Wang T, Fu J, Xiao G, Liu Y (2015) Nonoptimal codon usage influences protein structure in intrinsically disordered regions. Mol Microbiol 97:974–987
226. Chu D, Kazana E, Bellanger N, Singh T, Tuite MF, von der Haar T (2014) Translation elongation can control translation initiation on eukaryotic mRNAs. EMBO J 33:21–34