Skip to main content

Advertisement

Springer Nature Link
Log in

The many facets of H/ACA ribonucleoproteins

  • Review
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

The H/ACA ribonucleoproteins (RNPs) are known as one of the two major classes of small nucleolar RNPs. They predominantly guide the site-directed pseudouridylation of target RNAs, such as ribosomal and spliceosomal small nuclear RNAs. In addition, they process ribosomal RNA and stabilize vertebrate telomerase RNA. Taken together, the function of H/ACA RNPs is essential for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. Every cell contains 100–200 different species of H/ACA RNPs, each consisting of the same four core proteins and one function-specifying H/ACA RNA. Most of these RNPs reside in nucleoli and Cajal bodies and mediate the isomerization of specific uridines to pseudouridines. Catalysis of the reaction is mediated by the putative pseudouridylase NAP57 (dyskerin, Cbf5p). Unexpectedly, mutations in this housekeeping enzyme are the major determinants of the inherited bone marrow failure syndrome dyskeratosis congenita. This review details the many diverse functions of H/ACA RNPs, some yet to be uncovered, with an emphasis on the role of the RNP proteins. The multiple functions of H/ACA RNPs appear to be reflected in the complex phenotype of dyskeratosis congenita.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2a,b
Fig. 3a,b
Fig. 4a–d

Similar content being viewed by others

References

  • Aravind L, Koonin EV (1999) Novel predicted RNA-binding domains associated with the translation machinery. J Mol Evol 48:291–302

    Google Scholar 

  • 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

    Google Scholar 

  • Atzorn V, Fragapane P, Kiss T (2004) U17/snR30 is a ubiquitous snoRNA with two conserved sequence motifs essential for 18S rRNA production. Mol Cell Biol 24:1769–1778

    Google Scholar 

  • Bachellerie JP, Cavaille J, Huttenhofer A (2002) The expanding snoRNA world. Biochimie 84:775–790

    Article  CAS  PubMed  Google Scholar 

  • Badis G, Fromont-Racine M, Jacquier A (2003) A snoRNA that guides the two most conserved pseudouridine modifications within rRNA confers a growth advantage in yeast. RNA 9:771–779

    Google Scholar 

  • Bagni C, Lapeyre B (1998) Gar1p binds to the small nucleolar RNAs snR10 and snR30 in vitro through a nontypical RNA binding element. J Biol Chem 273:10868–10873

    Google Scholar 

  • Bakin A, Lane BG, Ofengand J (1994) Clustering of pseudouridine residues around the peptidyltransferase center of yeast cytoplasmic and mitochondrial ribosomes. Biochemistry 33:13475–13483

    Google Scholar 

  • 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

    Google Scholar 

  • Bally M, Hughes J, Cesareni G (1988) SnR30: a new, essential small nuclear RNA from Saccharomyces cerevisiae. Nucleic Acids Res 16:5291–5303

    Google Scholar 

  • Behm-Ansmant I, Urban A, Ma X, Yu YT, Motorin Y, Branlant C (2003) The Saccharomyces cerevisiae U2 snRNA: pseudouridine-synthase Pus7p is a novel multisite–multisubstrate RNA: psi-synthase also acting on tRNAs. RNA 9:1371–1382

    Article  Google Scholar 

  • Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91:25–34

    Article  CAS  PubMed  Google Scholar 

  • Bortolin ML, Bachellerie JP, Clouet-d’Orval B (2003) In vitro RNP assembly and methylation guide activity of an unusual box C/D RNA, cis-acting archaeal pre-tRNA(Trp). Nucleic Acids Res 31:6524–6535

    Google Scholar 

  • Bousquet-Antonelli C, Henry Y, Gélugne J-P, Caizergues-Ferrer M, Kiss T (1997) A small nucleolar RNP protein is required for pseudouridylation of eukaryotic ribosomal RNAs. EMBO J 16:4770–4776

    Google Scholar 

  • Brand RC, Klootwijk J, Sibum CP, Planta RJ (1979) Pseudouridylation of yeast ribosomal precursor RNA. Nucleic Acids Res 7:121–134

    Google Scholar 

  • Burke B, Stewart CL (2002) Life at the edge: the nuclear envelope and human disease. Nat Rev Mol Cell Biol 3:575–585

    Google Scholar 

  • Cadwell C, Yoon H-J, Zebarjadian Y, Carbon J (1997) The yeast nucleolar protein Cbf5p is involved in rRNA biosynthesis and interacts genetically with the RNA polymerase I transcription factor RRN3. Mol Cell Biol 17:6175–6183

    Google Scholar 

  • 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

    Google Scholar 

  • Cervelli M, Oliverio M, Bellini A, Bologna M, Cecconi F, Mariottini P (2003) Structural and sequence evolution of U17 small nucleolar RNA (snoRNA) and its phylogenetic congruence in chelonians. J Mol Evol 57:73–84

    Google Scholar 

  • Charette M, Gray MW (2000) Pseudouridine in RNA: what, where, how, and why. IUBMB Life 49:341–351

    Google Scholar 

  • Chen HK, Pai CY, Huang JY, Yeh NH (1999) Human Nopp140, which interacts with RNA polymerase I: implications for rRNA gene transcription and nucleolar structural organization. Mol Cell Biol 19:8536–8546

    Google Scholar 

  • Chiu CM, Tsay YG, Chang CJ, Lee SC (2002) Nopp140 is a mediator of the protein kinase A signaling pathway that activates the acute phase response alpha1-acid glycoprotein gene. J Biol Chem 277:39102–39111

    Google Scholar 

  • Cmejla R, Blafkova J, Stopka T, Zavadil J, Pospisilova D, Mihal V, Petrtylova K, Jelinek J (2000) Ribosomal protein S19 gene mutations in patients with Diamond–Blackfan anemia and identification of ribosomal protein S19 pseudogenes. Blood Cells Mol Dis 26:124–132

    Google Scholar 

  • Cole HN, Rauschkolb JE, Toomey J (1930) Dyskeratosis congenita with pigmentation, dystrophy unguis and leukokeratosis oris. Arch Dermatol Syph 21:71–95

    Google Scholar 

  • Cong YS, Wright WE, Shay JW (2002) Human telomerase and its regulation. Microbiol Mol Biol Rev 66:407–425

    Google Scholar 

  • Darzacq X, Jady 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 21:2746–2756

    Article  Google Scholar 

  • Davis DR (1995) Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res 23:5020–5026

    Google Scholar 

  • Decatur WA, Fournier MJ (2002) rRNA modifications and ribosome function. Trends Biochem Sci 27:344–351

    Article  Google Scholar 

  • Decatur WA, Fournier MJ (2003) RNA-guided nucleotide modification of ribosomal and other RNAs. J Biol Chem 278:695–698

    Article  Google Scholar 

  • de Lange T (2002) Protection of mammalian telomeres. Oncogene 21:532–540

    Article  PubMed  Google Scholar 

  • Dez C, Henras A, Faucon B, Lafontaine D, Caizergues-Ferrer M, Henry Y (2001) Stable expression in yeast of the mature form of human telomerase RNA depends on its association with the box H/ACA small nucleolar RNP proteins Cbf5p, Nhp2p and Nop10p. Nucleic Acids Res 29:598–603

    Google Scholar 

  • Dez C, Noaillac-Depeyre J, Caizergues-Ferrer M, Henry Y (2002) Naf1p, an essential nucleoplasmic factor specifically required for accumulation of box H/ACA small nucleolar RNPs. Mol Cell Biol 22:7053–7065

    Google Scholar 

  • Dokal I (2000) Dyskeratosis congenita in all its forms. Br J Haematol 110:768–779

    Google Scholar 

  • Dokal I, Vulliamy T (2003) Dyskeratosis congenita: its link to telomerase and aplastic anaemia. Blood Rev 17:217–225

    Article  PubMed  Google Scholar 

  • Donmez G, Hartmuth K, Luhrmann R (2004) Modified nucleotides at the 5′ end of human U2 snRNA are required for spliceosomal E-complex formation. RNA 10:1925–1933

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N (1999) The gene encoding ribosomal protein S19 is mutated in Diamond–Blackfan anaemia. Nat Genet 21:169–175

    Google Scholar 

  • Engmann MF (1926) A unique case of reticular pigmentation of the skin with atrophy. Arch Dermatol Syph 13:685–687

    Google Scholar 

  • Fatica A, Dlakic M, Tollervey D (2002) Naf1 p is a box H/ACA snoRNP assembly factor. RNA 8:1502–1514

    Google Scholar 

  • Filipowicz W, Pogacic V (2002) Biogenesis of small nucleolar ribonucleoproteins. Curr Opin Cell Biol 14:319–327

    Article  CAS  PubMed  Google Scholar 

  • Fortes P, Kufel J, Fornerod M, Polycarpou-Schwarz M, Lafontaine D, Tollervey D, Mattaj IW (1999) Genetic and physical interactions involving the yeast nuclear cap-binding complex. Mol Cell Biol 19:6543–6553

    Google Scholar 

  • Ganot P, Bortolin M-L, Kiss T (1997a) Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell 89:799–809

    Google Scholar 

  • Ganot P, Caizergues-Ferrer M, Kiss T (1997b) The family of box ACA small nucleolar RNAs is defined by an evolutionarily conserved secondary structure and ubiquitous sequence elements essential for RNA accumulation. Genes Dev 11:941–956

    Google Scholar 

  • Giordano E, Peluso I, Senger S, Furia M (1999) Minifly, a Drosophila gene required for ribosome biogenesis. J Cell Biol 144:1123–1133

    Google Scholar 

  • Girard J-P, 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

    Google Scholar 

  • Girard JP, Bagni C, Caizergues-Ferrer M, Amalric F, Lapeyre B (1994) Identification of a segment of the small nucleolar ribonucleoprotein-associated protein GAR1 that is sufficient for nucleolar accumulation. J Biol Chem 269:18499–18506

    Google Scholar 

  • 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

    Google Scholar 

  • Gubitz AK, Feng W, Dreyfuss G (2004) The SMN complex. Exp Cell Res 296:51–56

    Article  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Heiss NS, Girod A, Salowsky R, Wiemann S, Pepperkok R, Poustka A (1999) Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita. Hum Mol Genet 8:2515–2524

    Google Scholar 

  • 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

    Google Scholar 

  • Henras A, Dez C, Noaillac-Depeyre J, Henry Y, Caizergues-Ferrer M (2001) Accumulation of H/ACA snoRNPs depends on the integrity of the conserved central domain of the RNA-binding protein Nhp2p. Nucleic Acids Res 29:2733–2746

    Google Scholar 

  • Henras AK, Capeyrou R, Henry Y, Caizergues-Ferrer M (2004a) 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

    Google Scholar 

  • Henras AK, Dez C, Henry Y (2004b) RNA structure and function in C/D and H/ACA s(no)RNPs. Curr Opin Struct Biol 14:335–343

    Google Scholar 

  • Hoang C, Ferre-D’Amare AR (2001) Cocrystal structure of a tRNA Ψ55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107:929–939

    Google Scholar 

  • 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

    Google Scholar 

  • Hutchison CJ, Worman HJ (2004) A-type lamins: guardians of the soma? Nat Cell Biol 6:1062–1067

    Google Scholar 

  • Hüttenhofer 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

    Google Scholar 

  • Isaac C, Yang Y, Meier UT (1998) Nopp140 functions as a molecular link between the nucleolus and the coiled bodies. J Cell Biol 142:319–329

    Google Scholar 

  • Isaac C, Pollard JW, Meier UT (2001) Intranuclear endoplasmic reticulum induced by Nopp140 mimics the nucleolar channel system of human endometrium. J Cell Sci 114:4253–4264

    Google Scholar 

  • Jady 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 20:541–551

    Article  Google Scholar 

  • Jady BE, Bertrand E, Kiss T (2004) Human telomerase RNA and box H/ACA scaRNAs share a common Cajal body-specific localization signal. J Cell Biol 164:647–652

    Google Scholar 

  • Jeanteur P, Amaldi F, Attardi G (1968) Partial sequence analysis of ribosomal RNA from HeLa cells. II. Evidence for sequences of non-ribosomal type in 45 and 32 s ribosomal RNA precursors. J Mol Biol 33:757–775

    Google Scholar 

  • Jiang W, Middleton K, Yoon H-J, Fouquet C, Carbon J (1993) An essential yeast protein, CBF5p, binds in vitro to centromeres and microtubules. Mol Cell Biol 13:4884–4893

    Google Scholar 

  • Jones KW, Gorzynski K, Hales CM, Fischer U, Badbanchi F, Terns RM, Terns MP (2001) Direct interaction of the spinal muscular atrophy disease protein SMN with the small nucleolar RNA-associated protein fibrillarin. J Biol Chem 276:38645–38651

    Google Scholar 

  • Kato N, Harada F (1984) Nucleotide sequence of nuclear 5.4 S RNA of mouse cells. Biochim Biophys Acta 782:127–131

    Google Scholar 

  • Kauffman T, Tran J, DiNardo S (2003) Mutations in Nop60B, the Drosophila homolog of human dyskeratosis congenita 1, affect the maintenance of the germ-line stem cell lineage during spermatogenesis. Dev Biol 253:189–199

    Google Scholar 

  • Kendall A, Hull MW, Bertrand E, Good PD, Singer RH, Engelke DR (2000) A CBF5 mutation that disrupts nucleolar localization of early tRNA biosynthesis in yeast also suppresses tRNA gene-mediated transcriptional silencing. Proc Natl Acad Sci U S A 97:13108–13113

    Google Scholar 

  • 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

    Article  Google Scholar 

  • Kiss T (2002) Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell 109:145–148

    Google Scholar 

  • Kiss T (2004) Biogenesis of small nuclear RNPs. J Cell Sci 117:5949–5951

    Google Scholar 

  • Kiss T, Filipowicz W (1993) Small nucleolar RNAs encoded by introns of the human cell cycle regulatory gene RCC1. EMBO J 12:2913–2920

    Google Scholar 

  • Kiss AM, Jady BE, Darzacq X, Verheggen C, Bertrand E, Kiss T (2002) A Cajal body-specific pseudouridylation guide RNA is composed of two box H/ACA snoRNA-like domains. Nucleic Acids Res 30:4643–4649

    Article  Google Scholar 

  • Kiss AM, Jady BE, Bertrand E, Kiss T (2004) Human box H/ACA pseudouridylation guide RNA machinery. Mol Cell Biol 24:5797–5807

    Google Scholar 

  • Knight SW, Heiss NS, Vulliamy TJ, Greschner S, Stavrides G, Pai GS, Lestringant G, Varma N, Mason PJ, Dokal I, Poustka A (1999) X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am J Hum Genet 65:50–58

    Google Scholar 

  • Knight SW, Vulliamy TJ, Morgan B, Devriendt K, Mason PJ, Dokal I (2001) Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis. Hum Genet 108:299–303

    Google Scholar 

  • Kolodrubetz D, Haggren W, Burgum A (1988) Amino-terminal sequence of a Saccharomyces cerevisiae nuclear protein, NHP6, shows significant identity to bovine HMG1. FEBS Lett 238:175–179

    Google Scholar 

  • 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

    Google Scholar 

  • Lafontaine DL, Tollervey D (1998) Birth of the snoRNPs: the evolution of the modification-guide snoRNAs. Trends Biochem Sci 23:383–388

    Google Scholar 

  • Lafontaine DLJ, 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

    Google Scholar 

  • Leung AK, Lamond AI (2002) In vivo analysis of NHPX reveals a novel nucleolar localization pathway involving a transient accumulation in splicing speckles. J Cell Biol 157:615–629

    Google Scholar 

  • Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V, Cech TR (1997) Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276:561–567

    Article  PubMed  Google Scholar 

  • Lübben B, Fabrizio P, Kastner B, Lührmann R (1995) Isolation and characterization of the small nucleolar ribonucleoprotein particle snR30 from Saccharomyces cerevisiae. J Biol Chem 270:11549–11554

    Google Scholar 

  • Ma X, Zhao X, Yu YT (2003) Pseudouridylation (Psi) of U2 snRNA in S. cerevisiae is catalyzed by an RNA-independent mechanism. EMBO J 22:1889–1897

    Article  Google Scholar 

  • Maden BH (1990) The numerous modified nucleotides in eukaryotic ribosomal RNA. Prog Nucleic Acid Res Mol Biol 39:241–303

    Google Scholar 

  • Marrone A, Mason PJ (2003) Dyskeratosis congenita. Cell Mol Life Sci 60:507–517

    Article  CAS  PubMed  Google Scholar 

  • Massenet S, Mougin A, Branlant C (1998) Posttranscriptional modifications in the U small nuclear RNAs. In: Grosjean H, Benne R (eds) The modification and editing of RNA. ASM Press, Washington, DC, pp 201–228

    Google Scholar 

  • Massenet S, Motorin Y, Lafontaine DL, 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 19:2142–2154

    Google Scholar 

  • Meier UT (1996) Comparison of the rat nucleolar protein Nopp140 to its yeast homolog SRP40: differential phosphorylation in vertebrates and yeast. J Biol Chem 271:19376–19384

    Google Scholar 

  • Meier UT (2003) Dissecting dyskeratosis. Nat Genet 33:116–117

    Google Scholar 

  • Meier UT, Blobel G (1992) Nopp140 shuttles on tracks between nucleolus and cytoplasm. Cell 70:127–138

    Google Scholar 

  • Meier UT, Blobel G (1994) NAP57, a mammalian nucleolar protein with a putative homolog in yeast and bacteria. J Cell Biol 127:1505–1514, [correction appeared in 140:447]

    Google Scholar 

  • Meister G, Eggert C, Fischer U (2002) SMN-mediated assembly of RNPs: a complex story. Trends Cell Biol 12:472–478

    Article  Google Scholar 

  • Meroueh M, Grohar PJ, Qiu J, SantaLucia J Jr, 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 28:2075–2083

    Google Scholar 

  • Miau L-H, Chang C-J, Tsai W-H, Lee S-C (1997) Identification and characterization of a nucleolar phosphoprotein Nopp140, as a transcription factor. Mol Cell Biol 17:230–239

    Google Scholar 

  • Mitchell JR, Cheng J, Collins K (1999a) A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3′ end. Mol Cell Biol 19:567–576

    CAS  PubMed  Google Scholar 

  • Mitchell JR, Wood E, Collins K (1999b) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402:551–555

    Article  CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Morrissey JP, Tollervey D (1993) Yeast snR30 is a small nucleolar RNA required for 18S rRNA synthesis. Mol Cell Biol 13:2469–2477

    Google Scholar 

  • Newby MI, Greenbaum NL (2001) A conserved pseudouridine modification in eukaryotic U2 snRNA induces a change in branch-site architecture. RNA 7:833–845

    Article  Google Scholar 

  • Newby MI, Greenbaum NL (2002) Sculpting of the spliceosomal branch site recognition motif by a conserved pseudouridine. Nat Struct Biol 9:958–965

    Article  Google Scholar 

  • Ni J, Tien AL, Fournier MJ (1997) Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell 89:565–573

    Article  Google Scholar 

  • Nottrott S, Hartmuth K, Fabrizio P, Urlaub H, Vidovic I, Ficner R, Luhrmann R (1999) Functional interaction of a novel 15.5 kD [U4/U6.U5] tri-snRNP protein with the 5′ stem–loop of U4 snRNA. EMBO J 18:6119–6133

    Google Scholar 

  • Nurse K, Wrzesinski J, Bakin A, Lane BG, Ofengand J (1995) Purification, cloning, and properties of the tRNA Ψ55 synthase from Escherichia coli. RNA 1:102–112

    Google Scholar 

  • Ofengand J (2002) Ribosomal RNA pseudouridines and pseudouridine synthases. FEBS Lett 514:17–25

    Article  Google Scholar 

  • Parker R, Simmons T, Shuster EO, Siliciano PG, Guthrie C (1988) Genetic analysis of small nuclear RNAs in Saccharomyces cerevisiae: viable sextuple mutant. Mol Cell Biol 8:3150–3159

    Google Scholar 

  • Pellizzoni L, Baccon J, Charroux B, Dreyfuss G (2001) The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1. Curr Biol 11:1079–1088

    Google Scholar 

  • Phillips B, Billin AN, Cadwell C, Buchholz R, Erickson C, Merriam JR, Carbon J, Poole SJ (1998) The Nop60B gene of Drosophila encodes an essential nucleolar protein that functions in yeast. Mol Gen Genet 260:20–29

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Ramenghi U, Campagnoli MF, Garelli E, Carando A, Brusco A, Bagnara GP, Strippoli P, Izzi GC, Brandalise S, Riccardi R, Dianzani I (2000) Diamond–Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population. Blood Cells Mol Dis 26:417–422

    Google Scholar 

  • 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

    Google Scholar 

  • Reddy R, Henning D, Busch H (1979) Nucleotide sequence of nucleolar U3B RNA. J Biol Chem 254:11097–11105

    Google Scholar 

  • Richard P, Darzacq X, Bertrand E, Jady BE, Verheggen C, Kiss T (2003) A common sequence motif determines the Cajal body-specific localization of box H/ACA scaRNAs. EMBO J 22:4283–4293

    Google Scholar 

  • 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

    Google Scholar 

  • Ruff EA, Rimoldi OJ, Raghu B, Eliceiri GL (1993) Three small nucleolar RNAs of unique nucleotide sequences. Proc Natl Acad Sci U S A 90:635–638

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Salowsky R, Heiss NS, Benner A, Wittig R, Poustka A (2002) Basal transcription activity of the dyskeratosis congenita gene is mediated by Sp1 and Sp3 and a patient mutation in a Sp1 binding site is associated with decreased promoter activity. Gene 293:9–19

    Google Scholar 

  • Samarsky DA, Balakin AG, Fournier MJ (1995) Characterization of three new snRNAs from Saccharomyces cerevisiae: snR34, snR35 and snR36. Nucleic Acids Res 23:2548–2554

    Google Scholar 

  • Seto AG, Zaug AJ, Sobel SG, Wolin SL, Cech TR (1999) Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 401:177–180

    Google Scholar 

  • Singh SK, Gurha P, Tran EJ, Maxwell ES, Gupta R (2004) Sequential 2′-O-methylation of archaeal pre-tRNATrp nucleotides is guided by the intron-encoded but trans-acting box C/D ribonucleoprotein of pre-tRNA. J Biol Chem 279:47661–47671

    Article  Google Scholar 

  • Smith CM, Steitz JA (1997) Sno storm in the nucleolus: new roles for myriad small RNPs. Cell 89:669–672

    Google Scholar 

  • 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

    Google Scholar 

  • Terns MP, Terns RM (2001) Macromolecular complexes: SMN—the master assembler. Curr Biol 11:R862–R864

    Google Scholar 

  • Tischkowitz M, Dokal I (2004) Fanconi anaemia and leukaemia—clinical and molecular aspects. Br J Haematol 126:176–191

    Google Scholar 

  • Tran E, Brown J, Maxwell ES (2004) Evolutionary origins of the RNA-guided nucleotide-modification complexes: from the primitive translation apparatus? Trends Biochem Sci 29:343–350

    Article  Google Scholar 

  • Tremblay A, Lamontagne B, Catala M, Yam Y, Larose S, Good L, Elela SA (2002) A physical interaction between Gar1p and Rnt1pi is required for the nuclear import of H/ACA small nucleolar RNA-associated proteins. Mol Cell Biol 22:4792–4802

    Google Scholar 

  • 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

    Google Scholar 

  • Vulliamy TJ, Knight SW, Heiss NS, Smith OP, Poustka A, Dokal I, Mason PJ (1999) Dyskeratosis congenita caused by a 3′ deletion: germline and somatic mosaicism in a female carrier. Blood 94:1254–1260

    Google Scholar 

  • Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001a) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413:432–435

    Article  CAS  PubMed  Google Scholar 

  • Vulliamy TJ, Knight SW, Mason PJ, Dokal I (2001b) Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita. Blood Cells Mol Dis 27:353–357

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Meier UT (2004) Architecture and assembly of mammalian H/ACA small nucleolar and telomerase ribonucleoproteins. EMBO J 23:1857–1867

    Google Scholar 

  • Wang C, Query CC, Meier UT (2002) Immunopurified small nucleolar ribonucleoprotein particles pseudouridylate rRNA independently of their association with phosphorylated Nopp140. Mol Cell Biol 22:8457–8466

    Google Scholar 

  • Watanabe Y, Gray MW (2000) Evolutionary appearance of genes encoding proteins associated with box H/ACA snoRNAs: cbf5p in Euglena gracilis, an early diverging eukaryote, and candidate Gar1p and Nop10p homologs in archaebacteria. Nucleic Acids Res 28:2342–2352

    Google Scholar 

  • Watkins NJ, Gottschalk A, Neubauer G, Kastner B, Fabrizio P, Mann M, Lührmann R (1998) Cbf5p, a potential pseudouridine synthase, and Nhp2p, a putative RNA-binding protein, are present together with Gar1p in all box H/ACA-motif snoRNPs and constitute a common bipartite structure. RNA 4:1549–1568

    Google Scholar 

  • 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

    Google Scholar 

  • Watkins NJ, Dickmanns A, Luhrmann R (2002) Conserved stem II of the box C/D motif is essential for nucleolar localization and is required, along with the 15.5 K protein, for the hierarchical assembly of the box C/D snoRNP. Mol Cell Biol 22:8342–8352

    Google Scholar 

  • Watkins NJ, Lemm I, Ingelfinger D, Schneider C, Hossbach M, Urlaub H, Luhrmann R (2004) Assembly and maturation of the U3 snoRNP in the nucleoplasm in a large dynamic multiprotein complex. Mol Cell 16:789–798

    Google Scholar 

  • Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB (1997) Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat Genet 17:498–502

    CAS  PubMed  Google Scholar 

  • Whitehead SE, Jones KW, Zhang X, Cheng X, Terns RM, Terns MP (2002) Determinants of the interaction of the spinal muscular atrophy disease protein SMN with the dimethylarginine-modified box H/ACA small nucleolar ribonucleoprotein GAR1. J Biol Chem 277:48087–48093

    Google Scholar 

  • Willig TN, Draptchinskaia N, Dianzani I, Ball S, Niemeyer C, Ramenghi U, Orfali K, Gustavsson P, Garelli E, Brusco A, Tiemann C, Perignon JL, Bouchier C, Cicchiello L, Dahl N, Mohandas N, Tchernia G (1999) Mutations in ribosomal protein S19 gene and Diamond–Blackfan anemia: wide variations in phenotypic expression. Blood 94:4294–4306

    Google Scholar 

  • Wong JM, Kyasa MJ, Hutchins L, Collins K (2004) Telomerase RNA deficiency in peripheral blood mononuclear cells in X-linked dyskeratosis congenita. Hum Genet 115:448–455

    Google Scholar 

  • 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 Nopp140. Mol Biol Cell 11:567–577

    Google Scholar 

  • Yang PK, Rotondo G, Porras T, Legrain P, Chanfreau G (2002) The Shq1p.Naf1p complex is required for box H/ACA small nucleolar ribonucleoprotein particle biogenesis. J Biol Chem 277:45235–45242

    Google Scholar 

  • Youssoufian H, Gharibyan V, Qatanani M (1999) Analysis of epitope-tagged forms of the dyskeratosis congenital protein (dyskerin): identification of a nuclear localization signal. Blood Cells Mol Dis 25:305–309

    Google Scholar 

  • Yu YT, Shu MD, Steitz JA (1998) Modifications of U2 snRNA are required for snRNP assembly and pre-mRNA splicing. EMBO J 17:5783–5795

    Article  Google Scholar 

  • 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

    Google Scholar 

  • Zhao X, Yu YT (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 10:681–690

    Article  Google Scholar 

  • Zhao X, Li ZH, Terns RM, Terns MP, Yu YT (2002) An H/ACA guide RNA directs U2 pseudouridylation at two different sites in the branchpoint recognition region in Xenopus oocytes. RNA 8:1515–1525

    Google Scholar 

  • Zhu Y, Tomlinson RL, Lukowiak AA, Terns RM, Terns MP (2004) Telomerase RNA accumulates in Cajal bodies in human cancer cells. Mol Biol Cell 15:81–90

    Google Scholar 

  • Zinsser F (1910) Atrophia cutis reticularis com pigmentatione, dystrophia et leukoplakia oris. Ikonogr Dermatol 5:219–223

    Google Scholar 

Download references

Acknowledgements

This review is dedicated to the memory of Jim Ofengand. I thank Charles Query, Susan Smith, Jon Warner, and the members of my laboratory for critical comments on the manuscript and Nupur Kittur for performing the immunofluorescence experiments in Fig. 4. The work in the author’s laboratory is supported by grants from the American Cancer Society and the National Heart Lung and Blood Institute.

Author information

Authors and Affiliations

  1. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    U. Thomas Meier

Authors
  1. U. Thomas Meier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Thomas Meier.

Additional information

Communicated by E.A. Nigg

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meier, U.T. The many facets of H/ACA ribonucleoproteins. Chromosoma 114, 1–14 (2005). https://doi.org/10.1007/s00412-005-0333-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-005-0333-9

Keywords