Abstract
Posttranscriptional ribosomal RNA (rRNA) modifications are present in all organisms and appear to be essential for the control of protein synthesis in the majority of species. The isomerization of uridine to pseudouridine on rRNA has important implications not only for ribosome structure but also for ribosome function. Structural and functional studies of both prokaryotic and eukaryotic ribosomes have revealed that pseudouridylation may regulate ribosome activity by facilitating extensive rRNA conformational changes. Furthermore, recent findings indicate that pseudouridylation of rRNA has an important regulatory role in modulating gene expression of specific mRNAs at the translational level. In this chapter we will review several biophysical approaches that have been employed to study the role of rRNA pseudouridine modifications in translation control. Additionally, we will provide mechanistic insights into how pseudouridylation of rRNA, when deregulated, may alter the expression of specific mRNAs contributing to certain pathological features of human diseases. Finally, we will discuss our perspectives on several outstanding questions related to the role of rRNA modifications in translational control.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alawi F, Lee M (2007) DKC1 is an evolutionarily conserved c-Myc target. FASEB J 21:A1155
Alter BP, Giri N, Savage SA, Rosenberg PS (2009) Cancer in dyskeratosis congenita. Blood 113:6549–6557
Aravind L, Koonin EV (1999) Novel predicted RNA-binding domains associated with the translation machinery. J Mol Evol 48:291–302
Arena F, Ciliberto G, Ciampi S, Cortese R (1978) Purification of pseudouridylate synthetase I from Salmonella typhimurium. Nucleic Acids Res 5:4523–4536
Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW (2005) Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci U S A 102:15960–15964
Armistead J, Khatkar S, Meyer B, Mark BL, Patel N, Coghlan G, Lamont RE, Liu S, Wiechert J, Cattini PA, Koetter P, Wrogemann K, Greenberg CR, Entian KD, Zelinski T, Triggs-Raine B (2009) Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-Conradi syndrome. Am J Hum Genet 84:728–739
Arnez JG, Steitz TA (1994) Crystal structure of unmodified tRNA(Gln) complexed with glutaminyl-tRNA synthetase and ATP suggests a possible role for pseudo-uridines in stabilization of RNA structure. Biochemistry 33:7560–7567
Bachellerie JP, Cavaille J (1997) Guiding ribose methylation of rRNA. Trends Biochem Sci 22:257–261
Bachellerie JP, Cavaille J, Huttenhofer A (2002) The expanding snoRNA world. Biochimie 84:775–790
Baker DL, Youssef OA, Chastkofsky MI, Dy DA, Terns RM, Terns MP (2005) RNA-guided RNA modification: functional organization of the archaeal H/ACA RNP. Genes Dev 19:1238–1248
Balakin AG, Smith L, Fournier MJ (1996) The RNA world of the nucleolus: two major families of small RNAs defined by different box elements with related functions. Cell 86:823–834
Barna M, Pusic A, Zollo O, Costa M, Kondrashov N, Rego E, Rao PH, Ruggero D (2008) Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature 456:971–975
Basu A, Das P, Chaudhuri S, Bevilacqua E, Andrews J, Barik S, Hatzoglou M, Komar AA, Mazumder B (2011) Requirement of rRNA methylation for 80S ribosome assembly on a cohort of cellular internal ribosome entry sites. Mol Cell Biol 31(22):4482–4499
Batista LF, Pech MF, Zhong FL, Nguyen HN, Xie KT, Zaug AJ, Crary SM, Choi J, Sebastiano V, Cherry A, Giri N, Wernig M, Alter BP, Cech TR, Savage SA, Reijo Pera RA, Artandi SE (2011) Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474:399–402
Baudin-Baillieu A, Fabret C, Liang XH, Piekna-Przybylska D, Fournier MJ, Rousset JP (2009) Nucleotide modifications in three functionally important regions of the Saccharomyces cerevisiae ribosome affect translation accuracy. Nucleic Acids Res 37:7665–7677
Bellodi C, Kopmar N, Ruggero D (2010a) Deregulation of oncogene-induced senescence and p53 translational control in X-linked dyskeratosis congenita. EMBO J 29:1865–1876
Bellodi C, Krasnykh O, Haynes N, Theodoropoulou M, Peng G, Montanaro L, Ruggero D (2010b) Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer Res 70:6026–6035
Bessler M, Wilson DB, Mason PJ (2004) Dyskeratosis congenita and telomerase. Curr Opin Pediatr 16:23–28
Bortolin ML, Ganot P, Kiss T (1999) Elements essential for accumulation and function of small nucleolar RNAs directing site-specific pseudouridylation of ribosomal RNAs. EMBO J 18:457–469
Bousquet-Antonelli C, Henry Y, G’Elugne JP, Caizergues-Ferrer M, Kiss T (1997) A small nucleolar RNP protein is required for pseudouridylation of eukaryotic ribosomal RNAs. EMBO J 16:4770–4776
Brand RC, Klootwijk J, Van Steenbergen TJ, De Kok AJ, Planta RJ (1977) Secondary methylation of yeast ribosomal precursor RNA. Eur J Biochem 75:311–318
Brand RC, Klootwijk J, Planta RJ, Maden BE (1978) Biosynthesis of a hypermodified nucleotide in Saccharomyces carlsbergensis 17S and HeLa-cell 18S ribosomal ribonucleic acid. Biochem J 169:71–77
Buchhaupt M, Meyer B, Kotter P, Entian KD (2006) Genetic evidence for 18S rRNA binding and an Rps19p assembly function of yeast nucleolar protein Nep1p. Mol Genet Genomics 276:273–284
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
Castle JC, Armour CD, Lower M, Haynor D, Biery M, Bouzek H, Chen R, Jackson S, Johnson JM, Rohl CA, Raymond CK (2010) Digital genome-wide ncRNA expression, including SnoRNAs, across 11 human tissues using polyA-neutral amplification. PLoS One 5:e11779
Cavaille J, Nicoloso M, Bachellerie JP (1996) Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides. Nature 383:732–735
Cavaille J, Buiting K, Kiefmann M, Lalande M, Brannan CI, Horsthemke B, Bachellerie JP, Brosius J, Huttenhofer A (2000) Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci U S A 97:14311–14316
Charette M, Gray MW (2000) Pseudouridine in RNA: what, where, how, and why. IUBMB Life 49:341–351
Cohn WE (1959) 5-Ribosyl uracil, a carbon-carbon ribofuranosyl nucleoside in ribonucleic acids. Biochim Biophys Acta 32:569–571
Conrad J, Sun D, Englund N, Ofengand J (1998) The rluC gene of Escherichia coli codes for a pseudouridine synthase that is solely responsible for synthesis of pseudouridine at positions 955, 2504, and 2580 in 23S ribosomal RNA. J Biol Chem 273:18562–18566
Conrad J, Niu L, Rudd K, Lane BG, Ofengand J (1999) 16S ribosomal RNA pseudouridine synthase RsuA of Escherichia coli: deletion, mutation of the conserved Asp102 residue, and sequence comparison among all other pseudouridine synthases. RNA 5:751–763
Cortese R, Kammen HO, Spengler SJ, Ames BN (1974) Biosynthesis of pseudouridine in transfer ribonucleic acid. J Biol Chem 249:1103–1108
Costantino DA, Pfingsten JS, Rambo RP, Kieft JS (2008) tRNA-mRNA mimicry drives translation initiation from a viral IRES. Nat Struct Mol Biol 15:57–64
Darzacq X, Kittur N, Roy S, Shav-Tal Y, Singer RH, Meier UT (2006) Stepwise RNP assembly at the site of H/ACA RNA transcription in human cells. J Cell Biol 173:207–218
Davis DR (1995) Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res 23:5020–5026
Davis FF, Allen FW (1957) Ribonucleic acids from yeast which contain a fifth nucleotide. J Biol Chem 227:907–915
Davis DR, Veltri CA, Nielsen L (1998) An RNA model system for investigation of pseudouridine stabilization of the codon-anticodon interaction in tRNALys, tRNAHis and tRNATyr. J Biomol Struct Dyn 15:1121–1132
Decatur WA, Fournier MJ (2002) rRNA modifications and ribosome function. Trends Biochem Sci 27:344–351
Decatur WA, Fournier MJ (2003) RNA-guided nucleotide modification of ribosomal and other RNAs. J Biol Chem 278:695–698
Del Campo M, Kaya Y, Ofengand J (2001) Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli. RNA 7:1603–1615
Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A (2007) The expanding RNA polymerase III transcriptome. Trends Genet 23:614–622
Doi Y, Arakawa Y (2007) 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin Infect Dis 45:88–94
Dokal I (2000) Dyskeratosis congenita in all its forms. Br J Haematol 110:768–779
Dragon F, Pogacic V, Filipowicz W (2000) In vitro assembly of human H/ACA small nucleolar RNPs reveals unique features of U17 and telomerase RNAs. Mol Cell Biol 20:3037–3048
Duan J, Li L, Lu J, Wang W, Ye K (2009) Structural mechanism of substrate RNA recruitment in H/ACA RNA-guided pseudouridine synthase. Mol Cell 34:427–439
Ejby M, Sorensen MA, Pedersen S (2007) Pseudouridylation of helix 69 of 23S rRNA is necessary for an effective translation termination. Proc Natl Acad Sci U S A 104:19410–19415
Eschrich D, Buchhaupt M, Kotter P, Entian KD (2002) Nep1p (Emg1p), a novel protein conserved in eukaryotes and archaea, is involved in ribosome biogenesis. Curr Genet 40:326–338
Filipowicz W, Pogacic V (2002) Biogenesis of small nucleolar ribonucleoproteins. Curr Opin Cell Biol 14:319–327
Frischmeyer PA, Dietz HC (1999) Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 8:1893–1900
Ganapathi KA, Shimamura A (2008) Ribosomal dysfunction and inherited marrow failure. Br J Haematol 141:376–387
Ganot P, Bortolin ML, Kiss T (1997) Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell 89:799–809
Ge J, Rudnick DA, He J, Crimmins DL, Ladenson JH, Bessler M, Mason PJ (2010) Dyskerin ablation in mouse liver inhibits rRNA processing and cell division. Mol Cell Biol 30:413–422
Giordano E, Peluso I, Senger S, Furia M (1999) Minifly, a Drosophila gene required for ribosome biogenesis. J Cell Biol 144:1123–1133
Girard JP, Lehtonen H, Caizergues-Ferrer M, Amalric F, Tollervey D, Lapeyre B (1992) GAR1 is an essential small nucleolar RNP protein required for pre-rRNA processing in yeast. EMBO J 11:673–682
Granneman S, Baserga SJ (2004) Ribosome biogenesis: of knobs and RNA processing. Exp Cell Res 296:43–50
Grozdanov PN, Roy S, Kittur N, Meier UT (2009) SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs. RNA 15:1188–1197
Gu X, Yu M, Ivanetich KM, Santi DV (1998) Molecular recognition of tRNA by tRNA pseudouridine 55 synthase. Biochemistry 37:339–343
Gu X, Liu Y, Santi DV (1999) The mechanism of pseudouridine synthase I as deduced from its interaction with 5-fluorouracil-tRNA. Proc Natl Acad Sci U S A 96:14270–14275
Gustafsson C, Reid R, Greene PJ, Santi DV (1996) Identification of new RNA modifying enzymes by iterative genome search using known modifying enzymes as probes. Nucleic Acids Res 24:3756–3762
Gutgsell NS, Deutscher MP, Ofengand J (2005) The pseudouridine synthase RluD is required for normal ribosome assembly and function in Escherichia coli. RNA 11:1141–1152
Hamma T, Ferre-D’Amare AR (2006) Pseudouridine synthases. Chem Biol 13:1125–1135
Hamma T, Ferre-D’Amare AR (2010) The box H/ACA ribonucleoprotein complex: interplay of RNA and protein structures in post-transcriptional RNA modification. J Biol Chem 285:805–809
Hamma T, Reichow SL, Varani G, Ferre-D’Amare AR (2005) The Cbf5-Nop10 complex is a molecular bracket that organizes box H/ACA RNPs. Nat Struct Mol Biol 12:1101–1107
He J, Navarrete S, Jasinski M, Vulliamy T, Dokal I, Bessler M, Mason PJ (2002) Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenita, causes embryonic lethality in mice. Oncogene 21:7740–7744
Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, 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
Hellen CU, Sarnow P (2001) Internal ribosome entry sites in eukaryotic mRNA molecules. Genes Dev 15:1593–1612
Henras A, Henry Y, Bousquet-Antonelli C, Noaillac-Depeyre J, Gelugne JP, Caizergues-Ferrer M (1998) Nhp2p and Nop10p are essential for the function of H/ACA snoRNPs. EMBO J 17:7078–7090
Henras AK, Capeyrou R, Henry Y, Caizergues-Ferrer M (2004) Cbf5p, the putative pseudouridine synthase of H/ACA-type snoRNPs, can form a complex with Gar1p and Nop10p in absence of Nhp2p and box H/ACA snoRNAs. RNA 10:1704–1712
Higa-Nakamine S, Suzuki T, Uechi T, Chakraborty A, Nakajima Y, Nakamura M, Hirano N, Kenmochi N (2012) Loss of ribosomal RNA modification causes developmental defects in zebrafish. Nucleic Acids Res 40(1):391–398
Hoang C, Ferre-D’Amare AR (2001) Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107:929–939
Hoang C, Hamilton CS, Mueller EG, Ferre-D’Amare AR (2005) Precursor complex structure of pseudouridine synthase TruB suggests coupling of active site perturbations to an RNA-sequestering peripheral protein domain. Protein Sci 14:2201–2206
Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318–327
Hoyeraal HM, Lamvik J, Moe PJ (1970) Congenital hypoplastic thrombocytopenia and cerebral malformations in two brothers. Acta Paediatr Scand 59:185–191
Hreidarsson S, Kristjansson K, Johannesson G, Johannsson JH (1988) A syndrome of progressive pancytopenia with microcephaly, cerebellar hypoplasia and growth failure. Acta Paediatr Scand 77:773–775
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 37:344–351
Hunter AG, Woerner SJ, Montalvo-Hicks LD, Fowlow SB, Haslam RH, Metcalf PJ, Lowry RB (1979) The Bowen-Conradi syndrome—a highly lethal autosomal recessive syndrome of microcephaly, micrognathia, low birth weight, and joint deformities. Am J Med Genet 3:269–279
Huttenhofer A, Kiefmann M, Meier-Ewert S, O’Brien J, Lehrach H, Bachellerie JP, Brosius J (2001) RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse. EMBO J 20:2943–2953
Iglesias-Serret D, Pique M, Gil J, Pons G, Lopez JM (2003) Transcriptional and translational control of Mcl-1 during apoptosis. Arch Biochem Biophys 417:141–152
Ishitani R, Yokoyama S, Nureki O (2008) Structure, dynamics, and function of RNA modification enzymes. Curr Opin Struct Biol 18:330–339
Ito E, Konno Y, Toki T, Terui K (2010) Molecular pathogenesis in Diamond-Blackfan anemia. Int J Hematol 92:413–418
Jack K, Bellodi C, Landry DM, Niederer RO, Meskauskas A, Musalgaonkar S, Kopmar N, Krasnykh O, Dean AM, Thompson SR, Ruggero D, Dinman JD (2011) rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. Mol Cell 44:660–666
Jang SK, Krausslich HG, Nicklin MJ, Duke GM, Palmenberg AC, Wimmer E (1988) A segment of the 5′ nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol 62:2636–2643
Jiang W, Middleton K, Yoon HJ, Fouquet C, Carbon J (1993) An essential yeast protein, CBF5p, binds in vitro to centromeres and microtubules. Mol Cell Biol 13:4884–4893
Johnson L, Soll D (1970) In vitro biosynthesis of pseudouridine at the polynucleotide level by an enzyme extract from Escherichia coli. Proc Natl Acad Sci U S A 67:943–950
Kammen HO, Marvel CC, Hardy L, Penhoet EE (1988) Purification, structure, and properties of Escherichia coli tRNA pseudouridine synthase I. J Biol Chem 263:2255–2263
Karijolich J, Yu YT (2011) Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474:395–398
Kastan MB, Radin AI, Kuerbitz SJ, Onyekwere O, Wolkow CA, Civin CI, Stone KD, Woo T, Ravindranath Y, Craig RW (1991) Levels of p53 protein increase with maturation in human hematopoietic cells. Cancer Res 51:4279–4286
Kaya Y, Ofengand J (2003) A novel unanticipated type of pseudouridine synthase with homologs in bacteria, archaea, and eukarya. RNA 9:711–721
Khanna M, Wu H, Johansson C, Caizergues-Ferrer M, Feigon J (2006) Structural study of the H/ACA snoRNP components Nop10p and the 3′ hairpin of U65 snoRNA. RNA 12:40–52
King TH, Liu B, McCully RR, Fournier MJ (2003) Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center. Mol Cell 11:425–435
Kirwan M, Dokal I (2008) Dyskeratosis congenita: a genetic disorder of many faces. Clin Genet 73:103–112
Kiss T (2001) Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs. EMBO J 20:3617–3622
Kiss AM, Jady BE, Bertrand E, Kiss T (2004) Human box H/ACA pseudouridylation guide RNA machinery. Mol Cell Biol 24:5797–5807
Kiss T, Fayet-Lebaron E, Jady BE (2010) Box H/ACA small ribonucleoproteins. Mol Cell 37:597–606
Kiss-Laszlo Z, Henry Y, Bachellerie JP, Caizergues-Ferrer M, Kiss T (1996) Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell 85:1077–1088
Klimasauskas S, Kumar S, Roberts RJ, Cheng X (1994) HhaI methyltransferase flips its target base out of the DNA helix. Cell 76:357–369
Kolodrubetz D, Burgum A (1991) Sequence and genetic analysis of NHP2: a moderately abundant high mobility group-like nuclear protein with an essential function in Saccharomyces cerevisiae. Yeast 7:79–90
Kondrashov N, Pusic A, Stumpf CR, Shimizu K, Hsieh AC, Xue S, Ishijima J, Shiroishi T, Barna M (2011) Ribosome-mediated specificity in hox mRNA translation and vertebrate tissue patterning. Cell 145:383–397
Koonin EV (1996) Pseudouridine synthases: four families of enzymes containing a putative uridine-binding motif also conserved in dUTPases and dCTP deaminases. Nucleic Acids Res 24:2411–2415
Krastev DB, Slabicki M, Paszkowski-Rogacz M, Hubner NC, Junqueira M, Shevchenko A, Mann M, Neugebauer KM, Buchholz F (2011) A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly. Nat Cell Biol 13:809–818
Krichevsky AM, Metzer E, Rosen H (1999) Translational control of specific genes during differentiation of HL-60 cells. J Biol Chem 274:14295–14305
Lafontaine DLJ, Tollervey D (1999) Nop58p is a common component of the box C + D snoRNPs that is required for snoRNA stability. RNA 5:455–467
Lafontaine DL, Bousquet-Antonelli C, Henry Y, Caizergues-Ferrer M, Tollervey D (1998) The box H + ACA snoRNAs carry Cbf5p, the putative rRNA pseudouridine synthase. Genes Dev 12:527–537
Lang KJ, Kappel A, Goodall GJ (2002) Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia. Mol Biol Cell 13:1792–1801
LaRiviere FJ, Cole SE, Ferullo DJ, Moore MJ (2006) A late-acting quality control process for mature eukaryotic rRNAs. Mol Cell 24:619–626
Leader DJ, Clark GP, Watters J, Beven AF, Shaw PJ, Brown JW (1997) Clusters of multiple different small nucleolar RNA genes in plants are expressed as and processed from polycistronic pre-snoRNAs. EMBO J 16:5742–5751
Lestrade L, Weber MJ (2006) snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res 34:D158–D162
Levy S, Avni D, Hariharan N, Perry RP, Meyuhas O (1991) Oligopyrimidine tract at the 5′ end of mammalian ribosomal protein mRNAs is required for their translational control. Proc Natl Acad Sci U S A 88:3319–3323
Lewis SM, Holcik M (2008) For IRES trans-acting factors, it is all about location. Oncogene 27:1033–1035
Li L, Ye K (2006) Crystal structure of an H/ACA box ribonucleoprotein particle. Nature 443:302–307
Liang XH, Liu Q, Fournier MJ (2007) rRNA modifications in an intersubunit bridge of the ribosome strongly affect both ribosome biogenesis and activity. Mol Cell 28:965–977
Liang XH, Liu Q, Fournier MJ (2009) Loss of rRNA modifications in the decoding center of the ribosome impairs translation and strongly delays pre-rRNA processing. RNA 15: 1716–1728
Limbach PA, Crain PF, McCloskey JA (1994) Summary: the modified nucleosides of RNA. Nucleic Acids Res 22:2183–2196
Liu PC, Thiele DJ (2001) Novel stress-responsive genes EMG1 and NOP14 encode conserved, interacting proteins required for 40S ribosome biogenesis. Mol Biol Cell 12:3644–3657
Liu Y, Elf SE, Miyata Y, Sashida G, Huang G, Di Giandomenico S, Lee JM, Deblasio A, Menendez S, Antipin J, Reva B, Koff A, Nimer SD (2009) p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell 4:37–48
Long KS, Poehlsgaard J, Kehrenberg C, Schwarz S, Vester B (2006) The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob Agents Chemother 50:2500–2505
Luo Y, Li S (2007) Genome-wide analyses of retrogenes derived from the human box H/ACA snoRNAs. Nucleic Acids Res 35:559–571
Lyman SK, Gerace L, Baserga SJ (1999) Human Nop5/Nop58 is a component common to the box C/D small nucleolar ribonucleoproteins. RNA 5:1597–1604
Maden BE, Forbes J (1972) Standard and non standard products in combined T(1) plus pancreatic RNAase fingerprints of HeLa cell rRNA and its precursors. FEBS Lett 28:289–292
Maden BE, Salim M, Williamson R, Shepherd J (1972) Chemical studies on ribosomal ribonucleic acid and ribosome formation in HeLa cells. Biochem J 129:30P
Marsh JC, Will AJ, Hows JM, Sartori P, Darbyshire PJ, Williamson PJ, Oscier DG, Dexter TM, Testa NG (1992) “Stem cell” origin of the hematopoietic defect in dyskeratosis congenita. Blood 79:3138–3144
Maxwell ES, Fournier MJ (1995) The small nucleolar RNAs. Annu Rev Biochem 64:897–934
Meier UT (2006) How a single protein complex accommodates many different H/ACA RNAs. Trends Biochem Sci 31:311–315
Meyer B, Wurm JP, Kotter P, Leisegang MS, Schilling V, Buchhaupt M, Held M, Bahr U, Karas M, Heckel A, Bohnsack MT, Wohnert J, Entian KD (2011) The Bowen-Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Psi1191 in yeast 18S rRNA. Nucleic Acids Res 39:1526–1537
Miskimins WK, Wang G, Hawkinson M, Miskimins R (2001) Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation. Mol Cell Biol 21:4960–4967
Mitchell JR, Wood E, Collins K (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402:551–555
Mochizuki Y, He J, Kulkarni S, Bessler M, Mason PJ (2004) Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Proc Natl Acad Sci U S A 101:10756–10761
Montanaro L (2010) Dyskerin and cancer: more than telomerase. The defect in mRNA translation helps in explaining how a proliferative defect leads to cancer. J Pathol 222:345–349
Montanaro L, Calienni M, Bertoni S, Rocchi L, Sansone P, Storci G, Santini D, Ceccarelli C, Taffurelli M, Carnicelli D, Brigotti M, Bonafe M, Trere D, Derenzini M (2010) Novel dyskerin-mediated mechanism of p53 inactivation through defective mRNA translation. Cancer Res 70:4767–4777
Morrissey JP, Tollervey D (1993) Yeast snR30 is a small nucleolar RNA required for 18S rRNA synthesis. Mol Cell Biol 13:2469–2477
Motorin Y, Helm M (2011) RNA nucleotide methylation. Wiley Interdiscip Rev RNA 2:611–631
Mueller EG (2002) Chips off the old block. Nat Struct Biol 9:320–322
Nabavi S, Nazar RN (2008) U3 snoRNA promoter reflects the RNA’s function in ribosome biogenesis. Curr Genet 54:175–184
Narla A, Ebert BL (2010) Ribosomopathies: human disorders of ribosome dysfunction. Blood 115:3196–3205
Newton K, Petfalski E, Tollervey D, Caceres JF (2003) Fibrillarin is essential for early development and required for accumulation of an intron-encoded small nucleolar RNA in the mouse. Mol Cell Biol 23:8519–8527
Ni J, Tien AL, Fournier MJ (1997) Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell 89:565–573
Normand C, Capeyrou R, Quevillon-Cheruel S, Mougin A, Henry Y, Caizergues-Ferrer M (2006) Analysis of the binding of the N-terminal conserved domain of yeast Cbf5p to a box H/ACA snoRNA. RNA 12:1868–1882
Ofengand J (2002) Ribosomal RNA pseudouridines and pseudouridine synthases. FEBS Lett 514:17–25
Okazuka K, Wakabayashi Y, Kashihara M, Inoue J, Sato T, Yokoyama M, Aizawa S, Aizawa Y, Mishima Y, Kominami R (2005) p53 prevents maturation of T cell development to the immature CD4-CD8+ stage in Bcl11b−/− mice. Biochem Biophys Res Commun 328:545–549
Patton JR, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel-Ghodsian N (2005) Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. J Biol Chem 280:19823–19828
Pelletier J, Sonenberg N (1988) Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334:320–325
Piekna-Przybylska D, Decatur WA, Fournier MJ (2008) The 3D rRNA modification maps database: with interactive tools for ribosome analysis. Nucleic Acids Res 36:D178–D183
Pogacic V, Dragon F, Filipowicz W (2000) Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10. Mol Cell Biol 20:9028–9040
Pyronnet S, Dostie J, Sonenberg N (2001) Suppression of cap-dependent translation in mitosis. Genes Dev 15:2083–2093
Ramamurthy V, Swann SL, Paulson JL, Spedaliere CJ, Mueller EG (1999) Critical aspartic acid residues in pseudouridine synthases. J Biol Chem 274:22225–22230
Rashid R, Liang B, Baker DL, Youssef OA, He Y, Phipps K, Terns RM, Terns MP, Li H (2006) Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita. Mol Cell 21:249–260
Raychaudhuri S, Conrad J, Hall BG, Ofengand J (1998) A pseudouridine synthase required for the formation of two universally conserved pseudouridines in ribosomal RNA is essential for normal growth of Escherichia coli. RNA 4:1407–1417
Raychaudhuri S, Niu L, Conrad J, Lane BG, Ofengand J (1999) Functional effect of deletion and mutation of the Escherichia coli ribosomal RNA and tRNA pseudouridine synthase RluA. J Biol Chem 274:18880–18886
Reichow SL, Hamma T, Ferre-D’Amare AR, Varani G (2007) The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res 35:1452–1464
Richard P, Kiss T (2006) Integrating snoRNP assembly with mRNA biogenesis. EMBO Rep 7:590–592
Rozhdestvensky TS, Tang TH, Tchirkova IV, Brosius J, Bachellerie JP, Huttenhofer A (2003) Binding of L7Ae protein to the K-turn of archaeal snoRNAs: a shared RNA binding motif for C/D and H/ACA box snoRNAs in Archaea. Nucleic Acids Res 31:869–877
Ruggero D, Grisendi S, Piazza F, Rego E, Mari F, Rao PH, Cordon-Cardo C, Pandolfi PP (2003) Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 299:259–262
Salim M, Williamson R, Maden BE (1970) Methylated oligonucleotides from HeLa cell ribosomal and nucleolar RNA. FEBS Lett 12:109–113
Samuelsson T, Olsson M (1990) Transfer RNA pseudouridine synthases in Saccharomyces cerevisiae. J Biol Chem 265:8782–8787
Schimmang T, Tollervey D, Kern H, Frank R, Hurt EC (1989) A yeast nucleolar protein related to mammalian fibrillarin is associated with small nucleolar RNA and is essential for viability. EMBO J 8:4015–4024
Scott MS, Avolio F, Ono M, Lamond AI, Barton GJ (2009) Human miRNA precursors with box H/ACA snoRNA features. PLoS Comput Biol 5:e1000507
Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602
Shaulsky G, Goldfinger N, Peled A, Rotter V (1991) Involvement of wild-type p53 in pre-B-cell differentiation in vitro. Proc Natl Acad Sci U S A 88:8982–8986
Sherrill KW, Byrd MP, Van Eden ME, Lloyd RE (2004) BCL-2 translation is mediated via internal ribosome entry during cell stress. J Biol Chem 279:29066–29074
Slatter TL, Ganesan P, Holzhauer C, Mehta R, Rubio C, Williams G, Wilson M, Royds JA, Baird MA, Braithwaite AW (2010) p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors. Cell Death Differ 17:540–550
Smith CM, Steitz JA (1998) Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol 18:6897–6909
Spedaliere CJ, Ginter JM, Johnston MV, Mueller EG (2004) The pseudouridine synthases: revisiting a mechanism that seemed settled. J Am Chem Soc 126:12758–12759
Spriggs KA, Bushell M, Mitchell SA, Willis AE (2005) Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors. Cell Death Differ 12: 585–591
Stoneley M, Willis AE (2004) Cellular internal ribosome entry segments: structures, trans-acting factors and regulation of gene expression. Oncogene 23:3200–3207
Tollervey D, Lehtonen H, Carmo-Fonseca M, Hurt EC (1991) The small nucleolar RNP protein NOP1 (fibrillarin) is required for pre-rRNA processing in yeast. EMBO J 10:573–583
Tollervey D, Lehtonen H, Jansen R, Kern H, Hurt EC (1993) Temperature-sensitive mutations demonstrate roles for yeast fibrillarin in pre-rRNA processing, pre-rRNA methylation, and ribosome assembly. Cell 72:443–457
Tortoriello G, de Celis JF, Furia M (2010) Linking pseudouridine synthases to growth, development and cell competition. FEBS J 277:3249–3263
Tsukiyama T, Ishida N, Shirane M, Minamishima YA, Hatakeyama S, Kitagawa M, Nakayama K (2001) Down-regulation of p27Kip1 expression is required for development and function of T cells. J Immunol 166:304–312
Tycowski KT, Steitz JA (2001) Non-coding snoRNA host genes in Drosophila: expression strategies for modification guide snoRNAs. Eur J Cell Biol 80:119–125
van Riggelen J, Yetil A, Felsher DW (2010) MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10:301–309
Vitali P, Royo H, Seitz H, Bachellerie JP, Huttenhofer A, Cavaille J (2003) Identification of 13 novel human modification guide RNAs. Nucleic Acids Res 31:6543–6551
Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413:432–435
Vulliamy TJ, Marrone A, Knight SW, Walne A, Mason PJ, Dokal I (2006) Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood 107:2680–2685
Vulliamy T, Beswick R, Kirwan M, Marrone A, Digweed M, Walne A, Dokal I (2008) Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc Natl Acad Sci U S A 105:8073–8078
Walbott H, Machado-Pinilla R, Liger D, Blaud M, Rety S, Grozdanov PN, Godin K, van Tilbeurgh H, Varani G, Meier UT, Leulliot N (2011) The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic. Genes Dev 25:2398–2408
Walne AJ, Vulliamy T, Marrone A, Beswick R, Kirwan M, Masunari Y, Al-Qurashi FH, Aljurf M, Dokal I (2007) Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. Hum Mol Genet 16:1619–1629
Wang C, Meier UT (2004) Architecture and assembly of mammalian H/ACA small nucleolar and telomerase ribonucleoproteins. EMBO J 23:1857–1867
Watkins NJ, Gottschalk A, Neubauer G, Kastner B, Fabrizio P, Mann M, Luhrmann R (1998) Cbf5p, a potential pseudouridine synthase, and Nhp2p, a putative RNA-binding protein, are present together with Gar1p in all H BOX/ACA-motif snoRNPs and constitute a common bipartite structure. RNA 4:1549–1568
Watkins NJ, Segault V, Charpentier B, Nottrott S, Fabrizio P, Bachi A, Wilm M, Rosbash M, Branlant C, Luhrmann R (2000) A common core RNP structure shared between the small nucleolar box C/D RNPs and the spliceosomal U4 snRNP. Cell 103:457–466
Weber MJ (2006) Mammalian small nucleolar RNAs are mobile genetic elements. PLoS Genet 2:e205
Westman BJ, Verheggen C, Hutten S, Lam YW, Bertrand E, Lamond AI (2010) A proteomic screen for nucleolar SUMO targets shows SUMOylation modulates the function of Nop5/Nop58. Mol Cell 39:618–631
Wilson JE, Pestova TV, Hellen CU, Sarnow P (2000a) Initiation of protein synthesis from the A site of the ribosome. Cell 102:511–520
Wilson JE, Powell MJ, Hoover SE, Sarnow P (2000b) Naturally occurring dicistronic cricket paralysis virus RNA is regulated by two internal ribosome entry sites. Mol Cell Biol 20:4990–4999
Wolfraim LA, Letterio JJ (2005) Cutting edge: p27Kip1 deficiency reduces the requirement for CD28-mediated costimulation in naive CD8+ but not CD4+ T lymphocytes. J Immunol 174:2481–2484
Wu G, Xiao M, Yang C, Yu YT (2011) U2 snRNA is inducibly pseudouridylated at novel sites by Pus7p and snR81 RNP. EMBO J 30:79–89
Yaghmai R, Kimyai-Asadi A, Rostamiani K, Heiss NS, Poustka A, Eyaid W, Bodurtha J, Nousari HC, Hamosh A, Metzenberg A (2000) Overlap of dyskeratosis congenita with the Hoyeraal-Hreidarsson syndrome. J Pediatr 136:390–393
Yang Y, Isaac C, Wang C, Dragon F, Pogacic V, Meier UT (2000) Conserved composition of mammalian box H/ACA and box C/D small nucleolar ribonucleoprotein particles and their interaction with the common factor Nopp 140. Mol Biol Cell 11:567–577
Yarian CS, Basti MM, Cain RJ, Ansari G, Guenther RH, Sochacka E, Czerwinska G, Malkiewicz A, Agris PF (1999) Structural and functional roles of the N1- and N3-protons of psi at tRNA’s position 39. Nucleic Acids Res 27:3543–3549
Yoon A, Peng G, Brandenburger Y, Zollo O, Xu W, Rego E, Ruggero D (2006) Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Science 312:902–906
Yu CT, Allen FW (1959) Studies on an isomer of uridine isolated from ribonucleic acids. Biochim Biophys Acta 32:393–406
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 19:7461–7472
Acknowledgements
We are grateful to members of the Ruggero lab for many helpful discussions and to Kimhouy Tong for critically reviewing and editing this manuscript. We apologize to those whose work we were unable to cite. This work is supported by National Institutes of Health grants R01 HL085572 (D.R.) and R01 CA140456 (D.R.). Davide Ruggero is a Leukemia and Lymphoma Society Research Scholar. Cristian Bellodi is a Leukemia and Lymphoma Society (LLS) and Aplastic Anemia and Myelodysplastic Syndromes (MDS) International Foundation (AA&MDS IF) research fellow.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media New York
About this chapter
Cite this chapter
McMahon, M., Bellodi, C., Ruggero, D. (2012). The “Fifth” RNA Nucleotide: A Role for Ribosomal RNA Pseudouridylation in Control of Gene Expression at the Translational Level. In: Dinman, J. (eds) Biophysical approaches to translational control of gene expression. Biophysics for the Life Sciences, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3991-2_13
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3991-2_13
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3990-5
Online ISBN: 978-1-4614-3991-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)