1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genetics
  4. Volume 54, 2020
  5. Article

Annual Review of Genetics

Volume 54, 2020

Regulation and Function of RNA Pseudouridylation in Human Cells

Abstract

Recent advances in pseudouridine detection reveal a complex pseudouridine landscape that includes messenger RNA and diverse classes of noncoding RNA in human cells. The known molecular functions of pseudouridine, which include stabilizing RNA conformations and destabilizing interactions with varied RNA-binding proteins, suggest that RNA pseudouridylation could have widespread effects on RNA metabolism and gene expression. Here, we emphasize how much remains to be learned about the RNA targets of human pseudouridine synthases, their basis for recognizing distinct RNA sequences, and the mechanisms responsible for regulated RNA pseudouridylation. We also examine the roles of noncoding RNA pseudouridylation in splicing and translation and point out the potential effects of mRNA pseudouridylation on protein production, including in the context of therapeutic mRNAs.

Keyword(s): innate immunity, mRNA, pseudouridine, RNA modification, snRNA, translation, tRNA
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-112618-043830
2020-11-23
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/genet/54/1/annurev-genet-112618-043830.html?itemId=/content/journals/10.1146/annurev-genet-112618-043830&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Addepalli B, Limbach PA. 2011. Mass spectrometry-based quantification of pseudouridine in RNA. J. Am. Soc. Mass Spectrom. 22:81363–72
     [Google Scholar]
  2. 2. 
    Anderson BR, Muramatsu H, Nallagatla SR, Bevilacqua PC, Sansing LH et al. 2010. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res 38:175884–92
     [Google Scholar]
  3. 3. 
    Antonicka H, Choquet K, Lin Z, Gingras A, Kleinman CL, Shoubridge EA 2017. A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep 18:128–38
     [Google Scholar]
  4. 4. 
    Arnez JG, Steitz TA. 1994. Crystal structure of unmodified tRNAGln complexed with glutaminyl-tRNA synthetase and ATP suggests a possible role for pseudo-uridines in stabilization of RNA structure. Biochemistry 33:247560–67
     [Google Scholar]
  5. 5. 
    Arroyo JD, Jourdain AA, Calvo SE, Ballarano CA, Doench JG et al. 2016. A genome-wide CRISPR death screen identifies genes essential for oxidative phosphorylation. Cell Metab 24:6875–85
     [Google Scholar]
  6. 6. 
    Bakin A, Ofengand J. 1993. Four newly located pseudouridylate residues in Escherichia coli 23S ribosomal RNA are all at the peptidyltransferase center: analysis by the application of a new sequencing technique. Biochemistry 32:379754–62
     [Google Scholar]
  7. 7. 
    Bare L, Uhlenbeck OC. 1985. Aminoacylation of anticodon loop-substituted yeast tyrosine transfer RNA. Biochemistry 24:92354–60
     [Google Scholar]
  8. 8. 
    Basak A, Query CC. 2014. A pseudouridine residue in the spliceosome core is part of the filamentous growth program in yeast. Cell Rep 8:4966–73
     [Google Scholar]
  9. 9. 
    Bertram K, Agafonov DE, Dybkov O, Haselbach D, Leelaram MN et al. 2017. Cryo-EM structure of a pre-catalytic human spliceosome primed for activation. Cell 170:4701–13.e11
     [Google Scholar]
  10. 10. 
    Boccaletto P, Machnicka MA, Purta E, Piątkowski P, Bagiński B et al. 2018. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res 46:D1D303–7
     [Google Scholar]
  11. 11. 
    Brandmayr C, Wagner M, Brückl T, Globisch D, Pearson D et al. 2012. Isotope-based analysis of modified tRNA nucleosides correlates modification density with translational efficiency. Angew. Chem. Int. Ed. 51:4411162–65
     [Google Scholar]
  12. 12. 
    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. 74:61303–8
     [Google Scholar]
  13. 13. 
    Carlile TM, Martinez NM, Schaening C, Su A, Bell TA et al. 2019. mRNA structure determines modification by pseudouridine synthase 1. Nat. Chem. Biol. 15:10966–74
     [Google Scholar]
  14. 14. 
    Carlile TM, Rojas-Duran MF, Gilbert WV 2015. Pseudo-Seq: genome-wide detection of pseudouridine modifications in RNA. Methods Enzymol 560:219–45
     [Google Scholar]
  15. 15. 
    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 515:7525143–46
     [Google Scholar]
  16. 16. 
    Chan C, Pham P, Dedon PC, Begley TJ 2018. Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol 19:1228
     [Google Scholar]
  17. 17. 
    Charenton C, Wilkinson ME, Nagai K 2019. Mechanism of 5′ splice site transfer for human spliceosome activation. Science 364:6438362–67
     [Google Scholar]
  18. 18. 
    Charette M, Gray MW. 2000. Pseudouridine in RNA: what, where, how, and why. IUBMB Life 49:5341–51
     [Google Scholar]
  19. 19. 
    Chen C, Zhao X, Kierzek R, Yu Y-T 2010. A flexible RNA backbone within the polypyrimidine tract is required for U2AF65 binding and pre-mRNA splicing in vivo. Mol. Cell. Biol 30:174108–19
     [Google Scholar]
  20. 20. 
    Chou H-J, Donnard E, Gustafsson HT, Garber M, Rando OJ 2017. Transcriptome-wide analysis of roles for tRNA modifications in translational regulation. Mol. Cell 68:5978–92.e4
     [Google Scholar]
  21. 21. 
    Chow KT, Gale M, Loo Y-M 2018. RIG-I and other RNA sensors in antiviral immunity. Annu. Rev. Immunol. 36:667–94
     [Google Scholar]
  22. 22. 
    Courtes FC, Gu C, Wong NSC, Dedon PC, Yap MGS, Lee D-Y 2014. 28S rRNA is inducibly pseudouridylated by the mTOR pathway translational control in CHO cell cultures. J. Biotechnol. 174:16–21
     [Google Scholar]
  23. 23. 
    Cozen AE, Quartley E, Holmes AD, Hrabeta-Robinson E, Phizicky EM, Lowe TM 2015. ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nat. Methods 12:9879–84
     [Google Scholar]
  24. 24. 
    Czudnochowski N, Wang AL, Finer-Moore J, Stroud RM 2013. In human pseudouridine synthase 1 (hPus1), a C-terminal helical insert blocks tRNA from binding in the same orientation as in the Pus1 bacterial homologue TruA, consistent with their different target selectivities. J. Mol. Biol. 425:203875–87
     [Google Scholar]
  25. 25. 
    Darzacq X, Jády BE, Verheggen C, Kiss AM, Bertrand E, Kiss T 2002. Cajal body-specific small nuclear RNAs: a novel class of 2′-O-methylation and pseudouridylation guide RNAs. EMBO J 21:112746–56
     [Google Scholar]
  26. 26. 
    Davis DR. 1995. Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res 23:245020–26
     [Google Scholar]
  27. 27. 
    Davis FF, Allen FW. 1957. Ribonucleic acids from yeast which contain a fifth nucleotide. J. Biol. Chem. 227:2907–15
     [Google Scholar]
  28. 28. 
    de Brouwer APM, Abou Jamra R, Körtel N, Soyris C, Polla DL et al. 2018. Variants in PUS7 cause intellectual disability with speech delay, microcephaly, short stature, and aggressive behavior. Am. J. Hum. Genet. 103:61045–52
     [Google Scholar]
  29. 29. 
    de Crécy-Lagard V, Boccaletto P, Mangleburg CG, Sharma P, Lowe TM et al. 2019. Matching tRNA modifications in humans to their known and predicted enzymes. Nucleic Acids Res 47:52143–59
     [Google Scholar]
  30. 30. 
    De Zoysa MD, Wu G, Katz R, Yu Y-T 2018. Guide-substrate base-pairing requirement for box H/ACA RNA-guided RNA pseudouridylation. RNA 24:81106–17
     [Google Scholar]
  31. 31. 
    Deb I, Popenda Ł, Sarzyńska J, Małgowska M, Lahiri A et al. 2019. Computational and NMR studies of RNA duplexes with an internal pseudouridine-adenosine base pair. Sci. Rep. 9:116278
     [Google Scholar]
  32. 32. 
    deLorimier E, Coonrod LA, Copperman J, Taber A, Reister EE et al. 2014. Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model. Nucleic Acids Res 42:2012768–78
     [Google Scholar]
  33. 33. 
    deLorimier E, Hinman MN, Copperman J, Datta K, Guenza M, Berglund JA 2017. Pseudouridine modification inhibits Muscleblind-like 1 (MBNL1) binding to CCUG repeats and minimally structured RNA through reduced RNA flexibility. J. Biol. Chem. 292:104350–57
     [Google Scholar]
  34. 34. 
    Deryusheva S, Choleza M, Barbarossa A, Gall JG, Bordonne R 2012. Post-transcriptional modification of spliceosomal RNAs is normal in SMN-deficient cells. RNA 18:131–36
     [Google Scholar]
  35. 35. 
    Deryusheva S, Gall JG. 2009. Small Cajal body-specific RNAs of Drosophila function in the absence of Cajal bodies. Mol. Biol. Cell 20:245250–59
     [Google Scholar]
  36. 36. 
    Deryusheva S, Gall JG. 2017. Dual nature of pseudouridylation in U2 snRNA: Pus1p-dependent and Pus1p-independent activities in yeasts and higher eukaryotes. RNA 23:71060–67
     [Google Scholar]
  37. 37. 
    Desaulniers J-P, Chang Y-C, Aduri R, Abeysirigunawardena SC, SantaLucia J Jr, Chow CS 2008. Pseudouridines in rRNA helix 69 play a role in loop stacking interactions. Org. Biomol. Chem. 6:213892–95
     [Google Scholar]
  38. 38. 
    Didychuk AL, Butcher SE, Brow DA 2018. The life of U6 small nuclear RNA, from cradle to grave. RNA 24:4437–60
     [Google Scholar]
  39. 39. 
    Dönmez G, Hartmuth K, Lührmann R 2004. Modified nucleotides at the 5′ end of human U2 snRNA are required for spliceosomal E-complex formation. RNA 10:121925–33
     [Google Scholar]
  40. 40. 
    Durant PC, Davis DR. 1999. Stabilization of the anticodon stem-loop of tRNALys,3 by an A+-C base-pair and by pseudouridine J. Mol. Biol 285:1115–31
     [Google Scholar]
  41. 41. 
    Durbin AF, Wang C, Marcotrigiano J, Gehrke L 2016. RNAs containing modified nucleotides fail to trigger RIG-I conformational changes for innate immune signaling. mBio 7:5e00833–16
     [Google Scholar]
  42. 42. 
    Evans ME, Clark WC, Zheng G, Pan T 2017. Determination of tRNA aminoacylation levels by high-throughput sequencing. Nucleic Acids Res 45:14e133
     [Google Scholar]
  43. 43. 
    Eyler DE, Franco MK, Batool Z, Wu MZ, Dubuke ML et al. 2019. Pseudouridinylation of mRNA coding sequences alters translation. PNAS 116:4623068–74
     [Google Scholar]
  44. 44. 
    Fernández IS, Ng CL, Kelley AC, Wu G, Yu Y-T, Ramakrishnan V 2013. Unusual base pairing during the decoding of a stop codon by the ribosome. Nature 500:7460107–10
     [Google Scholar]
  45. 45. 
    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 anaemia (MLASA). J. Med. Genet. 44:3173–80
     [Google Scholar]
  46. 46. 
    Fleming AM, Alenko A, Kitt JP, Orendt AM, Flynn PF et al. 2019. Structural elucidation of bisulfite adducts to pseudouridine that result in deletion signatures during reverse transcription of RNA. J. Am. Chem. Soc. 141:4116450–60
     [Google Scholar]
  47. 47. 
    Freund M, Asang C, Kammler S, Konermann C, Krummheuer J et al. 2003. A novel approach to describe a U1 snRNA binding site. Nucleic Acids Res 31:236963–75
     [Google Scholar]
  48. 48. 
    Ganot P, Jády BE, Bortolin M-L, Darzacq X, Kiss T 1999. Nucleolar factors direct the 2′-O-ribose methylation and pseudouridylation of U6 spliceosomal RNA. Mol. Cell. Biol. 19:106906–17
     [Google Scholar]
  49. 49. 
    Ge J, Yu Y-T. 2013. RNA pseudouridylation: new insights into an old modification. Trends Biochem. Sci. 38:4210–18
     [Google Scholar]
  50. 50. 
    Gilham PT, Ho NWY. 1971. Reaction of pseudouridine and inosine with N-cyclohexyl-N′-β-(4-methylmorpholinium) ethylcarbodiimide. Biochemistry 10:203651–57
     [Google Scholar]
  51. 51. 
    Gong J, Shao D, Xu K, Lu Z, Lu ZJ et al. 2018. RISE: a database of RNA interactome from sequencing experiments. Nucleic Acids Res 46:D1D194–201
     [Google Scholar]
  52. 52. 
    Guzzi N, Cieśla M, Ngoc PCT, Lang S, Arora S et al. 2018. Pseudouridylation of tRNA-derived fragments steers translational control in stem cells. Cell 173:51204–16.e26
     [Google Scholar]
  53. 53. 
    Hall KB, McLaughlin LW. 1991. Properties of a U1/mRNA 5′ splice site duplex containing pseudouridine as measured by thermodynamic and NMR methods. Biochemistry 30:71795–801
     [Google Scholar]
  54. 54. 
    Hamma T, Ferré-D'Amaré AR. 2006. Pseudouridine synthases. Chem. Biol. 13:111125–35
     [Google Scholar]
  55. 55. 
    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 21:2188–201
     [Google Scholar]
  56. 56. 
    Henras AK, Plisson-Chastang C, Humbert O, Romeo Y, Henry Y 2017. Synthesis, function, and heterogeneity of snoRNA-guided posttranscriptional nucleoside modifications in eukaryotic ribosomal RNAs. Enzymes 41:169–213
     [Google Scholar]
  57. 57. 
    Hoang C, Chen J, Vizthum CA, Kandel JM, Hamilton CS et al. 2006. Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol. Cell 24:4535–45
     [Google Scholar]
  58. 58. 
    Hoang C, Ferré-D'Amaré AR. 2001. Cocrystal structure of a tRNA Ψ55 pseudouridine synthase. Cell 107:7929–39
     [Google Scholar]
  59. 59. 
    Hoernes TP, Clementi N, Faserl K, Glasner H, Breuker K et al. 2016. Nucleotide modifications within bacterial messenger RNAs regulate their translation and are able to rewire the genetic code. Nucleic Acids Res 44:2852–62
     [Google Scholar]
  60. 60. 
    Hoernes TP, Heimdörfer D, Köstner D, Faserl K, Nußbaumer F et al. 2019. Eukaryotic translation elongation is modulated by single natural nucleotide derivatives in the coding sequences of mRNAs. Genes 10:284
     [Google Scholar]
  61. 61. 
    Hornung V, Ellegast J, Kim S, Brzozka K, Jung A et al. 2006. 5′-triphosphate RNA is the ligand for RIG-I. Science 314:5801994–97
     [Google Scholar]
  62. 62. 
    Huang L, Pookanjanatavip M, Gu X, Santi DV 1998. A conserved aspartate of tRNA pseudouridine synthase is essential for activity and a probable nucleophilic catalyst. Biochemistry 37:1344–51
     [Google Scholar]
  63. 63. 
    Huber S, Leonardi A, Dedon P, Begley T 2019. The versatile roles of the tRNA epitranscriptome during cellular responses to toxic exposures and environmental stress. Toxics 7:117
     [Google Scholar]
  64. 64. 
    Hudson GA, Bloomingdale RJ, Znosko BM 2013. Thermodynamic contribution and nearest-neighbor parameters of pseudouridine-adenosine base pairs in oligoribonucleotides. RNA 19:111474–82
     [Google Scholar]
  65. 65. 
    Hur S, Stroud RM. 2007. How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA. Mol. Cell 26:2189–203
     [Google Scholar]
  66. 66. 
    Ingolia NT, Hussmann JA, Weissman JS 2019. Ribosome profiling: global views of translation. Cold Spring Harb. Perspect. Biol. 11:5a032698
     [Google Scholar]
  67. 67. 
    Ishida K, Kunibayashi T, Tomikawa C, Ochi A, Kanai T et al. 2011. Pseudouridine at position 55 in tRNA controls the contents of other modified nucleotides for low-temperature adaptation in the extreme-thermophilic eubacterium Thermus thermophilus. . Nucleic Acids Res 39:62304–18
     [Google Scholar]
  68. 68. 
    Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P 2011. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol. Cell 43:4613–23
     [Google Scholar]
  69. 69. 
    Jack K, Bellodi C, Landry DM, Niederer RO, Meskauskas A et al. 2011. rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. Mol. Cell 44:4660–66
     [Google Scholar]
  70. 70. 
    Jády BE, Darzacq X, Tucker KE, Matera AG, Bertrand E, Kiss T 2003. Modification of Sm small nuclear RNAs occurs in the nucleoplasmic Cajal body following import from the cytoplasm. EMBO J 22:81878–88
     [Google Scholar]
  71. 71. 
    Jády BE, Kiss T. 2001. A small nucleolar guide RNA functions both in 2′-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA. EMBO J 20:3541–51
     [Google Scholar]
  72. 72. 
    Jana S, Hsieh AC, Gupta R 2017. Reciprocal amplification of caspase-3 activity by nuclear export of a putative human RNA-modifying protein, PUS10 during TRAIL-induced apoptosis. Cell Death Dis 8:10e3093
     [Google Scholar]
  73. 73. 
    Ji X, Dadon DB, Abraham BJ, Lee TI, Jaenisch R et al. 2015. Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions. PNAS 112:123841–46
     [Google Scholar]
  74. 74. 
    Jia G, Fu Y, Zhao X, Dai Q, Zheng G et al. 2011. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7:12885–87
     [Google Scholar]
  75. 75. 
    Jiang J, Aduri R, Chow CS, SantaLucia J 2014. Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations. Nucleic Acids Res 42:63971–81
     [Google Scholar]
  76. 76. 
    Jiang J, Kharel DN, Chow CS 2015. Modulation of conformational changes in helix 69 mutants by pseudouridine modifications. Biophys. Chem. 200–201:48–55
     [Google Scholar]
  77. 77. 
    Jorjani H, Kehr S, Jedlinski DJ, Gumienny R, Hertel J et al. 2016. An updated human snoRNAome. Nucleic Acids Res 44:115068–82
     [Google Scholar]
  78. 78. 
    Karijolich J, Yu Y-T. 2011. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474:7351395–98
     [Google Scholar]
  79. 79. 
    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 23:2165–75
     [Google Scholar]
  80. 80. 
    Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H et al. 2008. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16:111833–40
     [Google Scholar]
  81. 81. 
    Keffer-Wilkes LC, Veerareddygari GR, Kothe U, Feigon J 2016. RNA modification enzyme TruB is a tRNA chaperone. PNAS 113:5014306–11
     [Google Scholar]
  82. 82. 
    Kelly EK, Czekay DP, Kothe U 2019. Base-pairing interactions between substrate RNA and H/ACA guide RNA modulate the kinetics of pseudouridylation, but not the affinity of substrate binding by H/ACA small nucleolar ribonucleoproteins. RNA 25:101393–404
     [Google Scholar]
  83. 83. 
    Kennedy SD, Bauer WJ, Wang W, Kielkopf CL 2019. Dynamic stacking of an expected branch point adenosine in duplexes containing pseudouridine-modified or unmodified U2 snRNA sites. Biochem. Biophys. Res. Commun. 511:2416–21
     [Google Scholar]
  84. 84. 
    Khoddami V, Yerra A, Mosbruger TL, Fleming AM, Burrows CJ, Cairns BR 2019. Transcriptome-wide profiling of multiple RNA modifications simultaneously at single-base resolution. PNAS 116:146784–89
     [Google Scholar]
  85. 85. 
    Kierzek E, Malgowska M, Lisowiec J, Turner DH, Gdaniec Z, Kierzek R 2014. The contribution of pseudouridine to stabilities and structure of RNAs. Nucleic Acids Res 42:53492–501
     [Google Scholar]
  86. 86. 
    Kiss AM, Jady BE, Bertrand E, Kiss T 2004. Human box H/ACA pseudouridylation guide RNA machinery. Mol. Cell. Biol. 24:135797–807
     [Google Scholar]
  87. 87. 
    Kiss T. 2001. Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs. EMBO J 20:143617–22
     [Google Scholar]
  88. 88. 
    Kligun E, Mandel-Gutfreund Y. 2015. The role of RNA conformation in RNA-protein recognition. RNA Biol 12:7720–27
     [Google Scholar]
  89. 89. 
    Kolev NG, Steitz JA. 2006. In vivo assembly of functional U7 snRNP requires RNA backbone flexibility within the Sm-binding site. Nat. Struct. Mol. Biol. 13:4347–53
     [Google Scholar]
  90. 90. 
    Lestrade L, Weber MJ. 2006. snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res 34:Suppl. 1D158–62
     [Google Scholar]
  91. 91. 
    Li S, Xu Z, Sheng J 2018. tRNA-derived small RNA: a novel regulatory small non-coding RNA. Genes 9:5246
     [Google Scholar]
  92. 92. 
    Li X, Ma S, Yi C 2016. Pseudouridine: the fifth RNA nucleotide with renewed interests. Curr. Opin. Chem. Biol. 33:108–16
     [Google Scholar]
  93. 93. 
    Li X, Zhu P, Ma S, Song J, Bai J et al. 2015. Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nat. Chem. Biol. 11:8592–97
     [Google Scholar]
  94. 94. 
    Lorenz C, Lünse C, Mörl M 2017. tRNA modifications: impact on structure and thermal adaptation. Biomolecules 7:435
     [Google Scholar]
  95. 95. 
    Lovejoy AF, Riordan DP, Brown PO 2014. Transcriptome-wide mapping of pseudouridines: Pseudouridine synthases modify specific mRNAs in S. cerevisiae. . PLOS ONE 9:10e110799
     [Google Scholar]
  96. 96. 
    Ma X, Zhao X, Yu Y-T 2003. Pseudouridylation (Ψ) of U2 snRNA in S. cerevisiae is catalyzed by an RNA-independent mechanism. EMBO J 22:81889–97
     [Google Scholar]
  97. 97. 
    MacRae AJ, Mayerle M, Hrabeta-Robinson E, Chalkley RJ, Guthrie C et al. 2018. Prp8 positioning of U5 snRNA is linked to 5′ splice site recognition. RNA 24:6769–77
     [Google Scholar]
  98. 98. 
    Martinez NM, Gilbert WV. 2018. Pre-mRNA modifications and their role in nuclear processing. Quant. Biol. 6:3210–27
     [Google Scholar]
  99. 99. 
    Massenet S, Branlant C. 1999. A limited number of pseudouridine residues in the human atac spliceosomal UsnRNAs as compared to human major spliceosomal UsnRNAs. RNA 5:111495–503
     [Google Scholar]
  100. 100. 
    Massenet S, Motorin Y, Lafontaine DLJ, Hurt EC, Grosjean H, Branlant C 1999. Pseudouridine mapping in the Saccharomyces cerevisiae spliceosomal U small nuclear RNAs (snRNAs) reveals that pseudouridine synthase Pus1p exhibits a dual substrate specificity for U2 snRNA and tRNA. Mol. Cell. Biol. 19:32142–54
     [Google Scholar]
  101. 101. 
    Mauger DM, Cabral BJ, Presnyak V, Su SV, Reid DW et al. 2019. mRNA structure regulates protein expression through changes in functional half-life. PNAS 116:4824075–83
     [Google Scholar]
  102. 102. 
    McCleverty CJ, Hornsby M, Spraggon G, Kreusch A 2007. Crystal structure of human Pus10, a novel pseudouridine synthase. J. Mol. Biol. 373:51243–54
     [Google Scholar]
  103. 103. 
    McMahon M, Contreras A, Holm M, Uechi T, Forester CM et al. 2019. A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS. eLife 8:e48847
     [Google Scholar]
  104. 104. 
    McMahon M, Contreras A, Ruggero D 2015. Small RNAs with big implications: new insights into H/ACA snoRNA function and their role in human disease. Wiley Interdiscip. Rev. RNA 6:2173–89
     [Google Scholar]
  105. 105. 
    Meier UT. 2017. RNA modification in Cajal bodies. RNA Biol 14:6693–700
     [Google Scholar]
  106. 106. 
    Meroueh M, Grohar PJ, Qiu J, SantaLucia J, Scaringe SA, Chow CS 2000. Unique structural and stabilizing roles for the individual pseudouridine residues in the 1920 region of Escherichia coli 23S rRNA. Nucleic Acids Res 28:102075–83
     [Google Scholar]
  107. 107. 
    Mitchell D, Assmann SM, Bevilacqua PC 2019. Probing RNA structure in vivo. Curr. Opin. Struct. Biol 59:151–58
     [Google Scholar]
  108. 108. 
    Nallagatla SR, Bevilacqua PC. 2008. Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner. RNA 14:61201–13
     [Google Scholar]
  109. 109. 
    Nallagatla SR, Jones CN, Ghosh SKB, Sharma SD, Cameron CE et al. 2013. Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR. PLOS ONE 8:3e57905
     [Google Scholar]
  110. 110. 
    Netzband R, Pager CT. 2019. Epitranscriptomic marks: emerging modulators of RNA virus gene expression. Wiley Interdiscip. Rev. RNA 11:3e1576
     [Google Scholar]
  111. 111. 
    Newby MI, Greenbaum NL. 2001. A conserved pseudouridine modification in eukaryotic U2 snRNA induces a change in branch-site architecture. RNA 7:6833–45
     [Google Scholar]
  112. 112. 
    Newman AJ, Norman C. 1992. U5 snRNA interacts with exon sequences at 5′ and 3′ splice sites. Cell 68:4743–54
     [Google Scholar]
  113. 113. 
    Nguyen THD, Galej WP, Bai X, Oubridge C, Newman AJ et al. 2016. Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution. Nature 530:7590298–302
     [Google Scholar]
  114. 114. 
    Nguyen THD, Galej WP, Bai X, Savva CG, Newman AJ et al. 2015. The architecture of the spliceosomal U4/U6.U5 tri-snRNP. Nature 523:755847–52
     [Google Scholar]
  115. 115. 
    Patton JR, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel-Ghodsian N 2005. Mitochondrial myopathy and sideroblastic anemia (MLASA). J. Biol. Chem. 280:2019823–28
     [Google Scholar]
  116. 116. 
    Penzo M, Montanaro L. 2018. Turning uridines around: role of rRNA pseudouridylation in ribosome biogenesis and ribosomal function. Biomolecules 8:238
     [Google Scholar]
  117. 117. 
    Raghunathan PL, Guthrie C. 1998. RNA unwinding in U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr. Biol. 8:15847–55
     [Google Scholar]
  118. 118. 
    Ramamurthy V, Swann SL, Paulson JL, Spedaliere CJ, Mueller EG 1999. Critical aspartic acid residues in pseudouridine synthases. J. Biol. Chem. 274:3222225–30
     [Google Scholar]
  119. 119. 
    Reddy R, Busch H. 1988. Small nuclear RNAs: RNA sequences, structure, and modifications. Structure and Function of Major and Minor Small Nuclear Ribonucleoprotein Particles ML Birnstiel 1–37 Berlin/Heidelberg, Ger: Springer
     [Google Scholar]
  120. 120. 
    Rhee H-W, Zou P, Udeshi ND, Martell JD, Mootha VK et al. 2013. Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science 339:61251328–31
     [Google Scholar]
  121. 121. 
    Richard P, Darzacq X, Bertrand E, Jády BE, Verheggen C, Kiss T 2003. A common sequence motif determines the Cajal body-specific localization of box H/ACA scaRNAs. EMBO J 22:164283–93
     [Google Scholar]
  122. 122. 
    Rintala-Dempsey AC, Kothe U. 2017. Eukaryotic stand-alone pseudouridine synthases—RNA modifying enzymes and emerging regulators of gene expression. ? RNA Biol 14:91185–96
     [Google Scholar]
  123. 123. 
    Roca X, Akerman M, Gaus H, Berdeja A, Bennett CF, Krainer AR 2012. Widespread recognition of 5′ splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes Dev 26:101098–109
     [Google Scholar]
  124. 124. 
    Roca X, Sachidanandam R, Krainer AR 2005. Determinants of the inherent strength of human 5′ splice sites. RNA 11:5683–98
     [Google Scholar]
  125. 125. 
    Rose RE, Quinn R, Sayre JL, Fabris D 2015. Profiling ribonucleotide modifications at full-transcriptome level: a step toward MS-based epitranscriptomics. RNA 21:71361–74
     [Google Scholar]
  126. 126. 
    Ross R, Cao X, Yu N, Limbach PA 2016. Sequence mapping of transfer RNA chemical modifications by liquid chromatography tandem mass spectrometry. Methods 107:73–78
     [Google Scholar]
  127. 127. 
    Safra M, Nir R, Farouq D, Vainberg Slutskin I, Schwartz S 2017. TRUB1 is the predominant pseudouridine synthase acting on mammalian mRNA via a predictable and conserved code. Genome Res 27:3393–406
     [Google Scholar]
  128. 128. 
    Scheunemann AE, Graham WD, Vendeix FAP, Agris PF 2010. Binding of aminoglycoside antibiotics to helix 69 of 23S rRNA. Nucleic Acids Res 38:93094–105
     [Google Scholar]
  129. 129. 
    Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH et al. 2014. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159:1148–62
     [Google Scholar]
  130. 130. 
    Senger B, Auxilien S, Englisch U, Cramer F, Fasiolo F 1997. The modified wobble base inosine in yeast tRNAIle is a positive determinant for aminoacylation by isoleucyl-tRNA synthetase. Biochemistry 36:278269–75
     [Google Scholar]
  131. 131. 
    Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA et al. 2014. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:616684–87
     [Google Scholar]
  132. 132. 
    Shi J, Zhang Y, Zhou T, Chen Q 2019. tsRNAs: the Swiss Army knife for translational regulation. Trends Biochem. Sci. 44:3185–89
     [Google Scholar]
  133. 133. 
    Sibert BS, Fischel-Ghodsian N, Patton JR 2008. Partial activity is seen with many substitutions of highly conserved active site residues in human Pseudouridine synthase 1. RNA 14:91895–906
     [Google Scholar]
  134. 134. 
    Sloan KE, Warda AS, Sharma S, Entian K-D, Lafontaine DLJ, Bohnsack MT 2017. Tuning the ribosome: the influence of rRNA modification on eukaryotic ribosome biogenesis and function. RNA Biol 14:91138–52
     [Google Scholar]
  135. 135. 
    Song J, Zhuang Y, Zhu C, Meng H, Lu B et al. 2020. Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation. Nat. Chem. Biol. 16:2160–69
     [Google Scholar]
  136. 136. 
    Spenkuch F, Motorin Y, Helm M 2014. Pseudouridine: still mysterious, but never a fake (uridine). ! RNA Biol 11:121540–54
     [Google Scholar]
  137. 137. 
    Stadler C, Rexhepaj E, Singan VR, Murphy RF, Pepperkok R et al. 2013. Immunofluorescence and fluorescent-protein tagging show high correlation for protein localization in mammalian cells. Nat. Methods 10:4315–23
     [Google Scholar]
  138. 138. 
    Sumita M, Jiang J, SantaLucia J, Chow CS 2012. Comparison of solution conformations and stabilities of modified helix 69 rRNA analogs from bacteria and human. Biopolymers 97:294–106
     [Google Scholar]
  139. 139. 
    Svidritskiy E, Madireddy R, Korostelev AA 2016. Structural basis for translation termination on a pseudouridylated stop codon. J. Mol. Biol. 428:102228–36
     [Google Scholar]
  140. 140. 
    Taoka M, Nobe Y, Yamaki Y, Sato K, Ishikawa H et al. 2018. Landscape of the complete RNA chemical modifications in the human 80S ribosome. Nucleic Acids Res 46:189289–98
     [Google Scholar]
  141. 141. 
    Tardu M, Jones JD, Kennedy RT, Lin Q, Koutmou KS 2019. Identification and quantification of modified nucleosides in Saccharomyces cerevisiae mRNAs. ACS Chem. Biol. 14:71403–9
     [Google Scholar]
  142. 142. 
    Taucher M, Ganisl B, Breuker K 2011. Identification, localization, and relative quantitation of pseudouridine in RNA by tandem mass spectrometry of hydrolysis products. Int. J. Mass Spectrom. 304:2–391–97
     [Google Scholar]
  143. 143. 
    Teigelkamp S, Newman AJ, Beggs JD 1995. Extensive interactions of PRP8 protein with the 5′ and 3′ splice sites during splicing suggest a role in stabilization of exon alignment by U5 snRNA. EMBO J 14:112602–12
     [Google Scholar]
  144. 144. 
    Tycowski KT, Shu M-D, Kukoyi A, Steitz JA 2009. A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. Mol. Cell 34:147–57
     [Google Scholar]
  145. 145. 
    Urban A, Behm-Ansmant I, Branlant C, Motorin Y 2009. RNA sequence and two-dimensional structure features required for efficient substrate modification by the Saccharomyces cerevisiae RNA:Ψ-synthase Pus7p. J. Biol. Chem. 284:95845–58
     [Google Scholar]
  146. 146. 
    Uzri D, Gehrke L. 2009. Nucleotide sequences and modifications that determine RIG-I/RNA binding and signaling activities. J. Virol. 83:94174–84
     [Google Scholar]
  147. 147. 
    Vaidyanathan PP, AlSadhan I, Merriman DK, Al-Hashimi HM, Herschlag D 2017. Pseudouridine and N6-methyladenosine modifications weaken PUF protein/RNA interactions. RNA 23:5611–18
     [Google Scholar]
  148. 148. 
    Veerareddygari GR, Singh SK, Mueller EG 2016. The pseudouridine synthases proceed through a glycal intermediate. J. Am. Chem. Soc. 138:257852–55
     [Google Scholar]
  149. 149. 
    Wan R, Yan C, Bai R, Wang L, Huang M et al. 2016. The 3.8 Å structure of the U4/U6.U5 tri-snRNP: insights into spliceosome assembly and catalysis. Science 351:6272466–75
     [Google Scholar]
  150. 150. 
    Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y et al. 2015. Identification and characterization of essential genes in the human genome. Science 350:62641096–101
     [Google Scholar]
  151. 151. 
    Wu CC-C, Zinshteyn B, Wehner KA, Green R 2019. High-resolution ribosome profiling defines discrete ribosome elongation states and translational regulation during cellular stress. Mol. Cell 73:5959–70.e5
     [Google Scholar]
  152. 152. 
    Wu G, Adachi H, Ge J, Stephenson D, Query CC, Yu Y 2016. Pseudouridines in U2 snRNA stimulate the ATPase activity of Prp5 during spliceosome assembly. EMBO J 35:6654–67
     [Google Scholar]
  153. 153. 
    Wu G, Huang C, Yu Y-T 2015. Pseudouridine in mRNA: incorporation, detection, and recoding. Methods Enzymol 560:187–217
     [Google Scholar]
  154. 154. 
    Wu G, Radwan MK, Xiao M, Adachi H, Fan J, Yu Y-T 2016. The TOR signaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA. RNA 22:81146–52
     [Google Scholar]
  155. 155. 
    Wu G, Xiao M, Yang C, Yu Y-T 2011. U2 snRNA is inducibly pseudouridylated at novel sites by Pus7p and snR81 RNP. EMBO J 30:179–89
     [Google Scholar]
  156. 156. 
    Yamauchi Y, Nobe Y, Izumikawa K, Higo D, Yamagishi Y et al. 2016. A mass spectrometry-based method for direct determination of pseudouridine in RNA. Nucleic Acids Res 44:6e59
     [Google Scholar]
  157. 157. 
    Yoon A, Peng G, Brandenburger Y, Brandenburg Y, Zollo O et al. 2006. Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Science 312:5775902–6
     [Google Scholar]
  158. 158. 
    Yu C-T, Allen FW. 1959. Studies of an isomer of uridine isolated from ribonucleic acids. Biochim. Biophys. Acta 32:393–406
     [Google Scholar]
  159. 159. 
    Zaganelli S, Rebelo-Guiomar P, Maundrell K, Rozanska A, Pierredon S et al. 2017. The pseudouridine synthase RPUSD4 is an essential component of mitochondrial RNA granules. J. Biol. Chem. 292:114519–32
     [Google Scholar]
  160. 160. 
    Zaher HS, Green R. 2009. Quality control by the ribosome following peptide bond formation. Nature 457:7226161–66
     [Google Scholar]
  161. 161. 
    Zaher HS, Green R. 2010. Kinetic basis for global loss of fidelity arising from mismatches in the P-site codon:anticodon helix. RNA 16:101980–89
     [Google Scholar]
  162. 162. 
    Zebarjadian Y, King T, Fournier MJ, Clarke L, Carbon J 1999. Point mutations in yeast CBF5 can abolish in vivo pseudouridylation of rRNA. Mol. Cell. Biol. 19:117461–72
     [Google Scholar]
  163. 163. 
    Zerby DB, Patton JR. 1996. Metabolism of pre-messenger RNA splicing cofactors: modification of U6 RNA is dependent on its interaction with U4 RNA. Nucleic Acids Res 24:183583–89
     [Google Scholar]
  164. 164. 
    Zerby DB, Patton JR. 1997. Modification of human U4 RNA requires U6 RNA and multiple pseudouridine synthases. Nucleic Acids Res 25:234808–15
     [Google Scholar]
  165. 165. 
    Zhang N, Shi S, Jia TZ, Ziegler A, Yoo B et al. 2019. A general LC-MS-based RNA sequencing method for direct analysis of multiple-base modifications in RNA mixtures. Nucleic Acids Res 47:20e125
     [Google Scholar]
  166. 166. 
    Zhang W, Eckwahl MJ, Zhou KI, Pan T 2019. Sensitive and quantitative probing of pseudouridine modification in mRNA and long noncoding RNA. RNA 25:91218–25
     [Google Scholar]
  167. 167. 
    Zhang X, Yan C, Hang J, Finci LI, Lei J, Shi Y 2017. An atomic structure of the human spliceosome. Cell 169:5918–29.e14
     [Google Scholar]
  168. 168. 
    Zhang X, Yan C, Zhan X, Li L, Lei J, Shi Y 2018. Structure of the human activated spliceosome in three conformational states. Cell Res 28:3307–22
     [Google Scholar]
  169. 169. 
    Zhao X, Yu Y-T. 2004. Pseudouridines in and near the branch site recognition region of U2 snRNA are required for snRNP biogenesis and pre-mRNA splicing in Xenopus oocytes. RNA 10:4681–90
     [Google Scholar]
  170. 170. 
    Zheng G, Qin Y, Clark WC, Dai Q, Yi C et al. 2015. Efficient and quantitative high-throughput tRNA sequencing. Nat. Methods 12:9835–37
     [Google Scholar]
  171. 171. 
    Zinshteyn B, Gilbert WV. 2013. Loss of a conserved tRNA anticodon modification perturbs cellular signaling. PLOS Genet 9:8e1003675
     [Google Scholar]
/content/journals/10.1146/annurev-genet-112618-043830
Loading
Regulation and Function of RNA Pseudouridylation in Human Cells
Annual Review of Genetics 54, 309 (2020); https://doi.org/10.1146/annurev-genet-112618-043830
/content/journals/10.1146/annurev-genet-112618-043830
/content/journals/10.1146/annurev-genet-112618-043830
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error