Skip to main content
SpringerLink
Log in

Eukaryotic ribosomal RNA: the recent excitement in the nucleotide modification problem

  • Chromosoma Focus
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

Eukaryotic ribosomal RNA (rRNA) contains numerous modified nucleotides: about 115 methyl groups and some 95 pseudouridines in vertebrates; about 65 methyl groups and some 45 pseudouridines inSaccharomyces cerevisiae. All but about ten of the methyl groups are ribose methylations. The remaining ten are on heterocyclic bases. The ribose methylations occur very rapidly upon the primary rRNA transcript in the nucleolus, prabably on nascent chains, and they appear to play an important role in ribosome maturation, at least in vertebrates. All of the methyl groups occur in the conserved core of rRNA. However, there is no consensus feature of sequence or secondary structure for the methylation sites; thus the nature of the signal(s) for site-specific methylations had until recently remained a mystery. The situation changed dramatically with the discovery that many of the ribose methylation sites are in regions that are precisely complementary to small nucleolar RNA (snoRNA) species. Experimental evidence indicates that structural motifs within the snoRNA species do indeed pinpoint the precise nucleotides to be methylated by the putative 2′-O-methyl transferase(s). Regarding base methylations, the geneDIM1, responsible for modification of the conserved dimethyladenosines near the 3′ end of 18S rRNA, has been shown to be essential for viability inS. cerevisiae and is suggested to play a role in the nucleocytoplasmic transport of the small ribosomal subunit. Recently nearly all of the pseudouridines have also been mapped in the rRNA of several eukaryotic species. As is the case for ribose methylations, most pseudouridine modifications occur rapidly upon precursor rRNA, within core sequences, and in a variety of local primary and secondary structure environments. In contrast to ribose methylation, no potentially unifying process has yet been identified for the enzymic recognition of the many pseudouridine modification sites. However, the new data afford the basis for a search for any potential involvement of snoRNAs in the recognition process.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bachellerie J-P,Michot B,Nicoloso M,Balakin A,Ni J,Fournier MJ (1995) Antisense snoRNAs: a family of nucleolar RNAs with long complementarities to rRNA. Trends Biochem Sci 20:261–264

    Article  PubMed  CAS  Google Scholar 

  • Bakin A, Ofengand J (1993) Four newly located pseudouridylate residues inEscherichia coli 23S ribosomal RNA are all at the peptidyl transfer center: analysis by a new sequencing technique. Biochemistry 32:9754–9762

    Article  PubMed  CAS  Google Scholar 

  • Bakin A, Kowalak JA,McCloskey JA,Ofengand J (1994a) The single pseudouridylate residue inE. coli 16S rRNA is located at position 516. Nucleic Acids Res 22:3681–3684

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Balakin AG,Schneider GS, Corbett MS, Ni JW, Fournier MJ (1993) SnR31, snR32, and snR33: three novel, nonessential snRNAs fromSaccharomyces cerevisiae. Nucleic Acids Res 21:5391–5397

    PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Beltrame M, Tollervey D (1995) Base pairing between U3 and the pre-ribosomal RNA is required for 18S rRNA synthesis. EMBO J 14:4350–4356

    PubMed  CAS  Google Scholar 

  • Brand RC, Klootwijk J, van Steenbergen TJM, de Kok AJ, Planta RJ (1977) Secondary methylation of yeast ribosomal precursor RNA. Eur J Biochem 75:311–318

    Article  PubMed  CAS  Google Scholar 

  • Brand RC, Klootwijk J, Planta RJ, Maden BEH (1978) Biosynthesis of a hypermodified nucleotide inSaccharomyces carlsbergensis 17S and HeLa cell 18S ribosomal ribonucleic acid. Biochem J 169:71–77

    PubMed  CAS  Google Scholar 

  • Caboche M, Bachellerie J-P (1977) RNA methylation and control of eukaryotic RNA biosynthesis. Effects of cycloleucine, a specific inhibitor of methylation, on ribosomal RNA maturation. Eur J Biochem 74:19–29

    Article  PubMed  CAS  Google Scholar 

  • Cavaillé J, Nicoloso M, Bachellerie J-P (1996). Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides. Nature 383:732–735

    Article  PubMed  Google Scholar 

  • Choi YC, Busch H (1978) Modified nucleotides in T1 RNase oligonucleotides of 18S ribosomal RNA of the Novikoff Hepatoma. Biochemistry 17:2551–2560

    Article  PubMed  CAS  Google Scholar 

  • Hadjiolov AA (1985) The nucleolus and ribosome biogenesis. In: Albert M, Beerman W, Goldstein L, Porter, KR, Sitte P (eds) Cell biology monographs. Springer, Vienna

    Google Scholar 

  • Helser TL, Davies JE, Dahlberg JE (1971) Change in methylation of 16S ribosomal RNA associated with mutation to kasugamycin resistance inEscherichia coli. Nature New Biol 233:12–14

    PubMed  CAS  Google Scholar 

  • Helser TL, Davies JE, Dahlberg JE (1972) Mechanism of kasugamycin resistance inEscherichia coli. Nature New Biol 235:6–9

    PubMed  CAS  Google Scholar 

  • Hughes, JMX (1991) Functional base-pairing interaction between highly conserved elements of U3 small nucleolar RNA and the small ribosomal subunit RNA. J Mol Biol 259:645–654

    Article  Google Scholar 

  • Hughes, JMX, Ares M (1991) Depletion of U3 small nucleolar RNA inhibits cleavage in the 5′ external transcribed spacer of yeast preribosomal RNA and prevents formation of 18S ribosomal RNA. EMBO J 10:4231–4239

    PubMed  CAS  Google Scholar 

  • Hughes JMX, Konings DAM, Cesareni G (1987) The yeast homologue of U3 snRNA. EMBO J 6:2145–2155

    PubMed  CAS  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 45S and 32S ribosomal RNA precursors. J Mol Biol 33:757–775

    Article  PubMed  CAS  Google Scholar 

  • Jeppesen C, Stebbins-Boaz B, Gerbi SA (1988) Nucleotide sequence determination and secondary structure ofXenopus U3 snRNA. Nucleic Acids Res 16:2127–2148

    PubMed  CAS  Google Scholar 

  • Kass S, Tyc K, Steitz JA, Sollner-Webb B (1990) The U3 small nucleolar ribonucleoprotein functions in the first step of pre-ribosomal RNA processing. Cell 60:897–908

    Article  PubMed  CAS  Google Scholar 

  • Kiss-László Z, Henry Y, Bachellerie J-P, Caizergues-Ferrer M, Kiss T (1996) Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell 85:1077–1088

    Article  PubMed  Google Scholar 

  • Lafontaine D, Delcour J, Glasser A-L, Desgrès J, Vandenhaute J (1994) TheDIM1 gene responsible for the conserved m 62 Am 62 A dimethylation in the 3′ terminal loop of 18S rRNA is essential in yeast. J Mol Biol 241:492–497

    Article  PubMed  CAS  Google Scholar 

  • Lafontaine D, Vandenhaute J, Tollervey D (1995) The 18S rRNA dimethylase Dim1p is required for pre-ribosomal RNA processing in yeast. Genes Dev 9:2470–2481

    PubMed  CAS  Google Scholar 

  • Lane BG, Ofengand J, Gray MW (1992) Pseudouridine in the large subunit (23S-like) ribosomal RNA. The site of peptidyl transfer in ribosome? FEBS Lett 302:1–4

    Article  PubMed  CAS  Google Scholar 

  • Lane BG, Ofengand J, Gray MW (1995) Pseudouridine and 2′-O-methylated nucleosides. Significance of their selective occurrence in rRNA domains that function in ribosome-catalyzed synthesis of the peptide bonds in proteins. Biochimie 77:7–15

    Article  PubMed  CAS  Google Scholar 

  • Li HV, Zagorski J, Fournier MJ (1990) Depletion of U14 snRNA (snR128) disrupts production of 18S ribosomal RNA synthesis inSaccharomyces cerevisiae. Mol Cell Biol 10:1145–1152

    PubMed  CAS  Google Scholar 

  • Liang W-Q, Fournier MJ (1995) U14 base-pairs with 18S rRNA: a novel snoRNA interaction required for rRNA processing. Genes Dev 9:2433–2443

    PubMed  CAS  Google Scholar 

  • Maden BEH (1986) Identification of the locations of the methyl groups in 18S ribosomal RNA fromXenopus laevis and man,. J Mol Biol 189:681–699

    Article  PubMed  CAS  Google Scholar 

  • Maden BEH (1988) Locations of methyl groups in 28S rRNA ofXenopus laevis and man: clustering in the conserved core of molecule. J Mol Biol 201:289–314

    Article  PubMed  CAS  Google Scholar 

  • Maden BEH (1990a) The modified nucleotides in ribosomal RNA of man and other eukaryotes. In: Gehrke CW, Kuo KCT (eds) Chromatography and modification of nucleosides part B: biological roles and function of modification. Elsevier, Amsterdam, pp B265–301

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Maden BEH, Salim M (1974) The methylated nucleotide sequences in HeLa cell ribosomal RNA and its precursors. J Mol Biol 88:133–164

    Article  PubMed  CAS  Google Scholar 

  • Maden BEH, Wakeman JA (1988) Pseudouridine distribution in mammalian 18S ribosomal RNA: a major cluster in the central region of the molecule. Biochem J 249:459–464

    PubMed  CAS  Google Scholar 

  • Maden BEH, Vaughan MH, Warner JR, Darnell JE (1969) Effects of valine deprivation on ribosome formation in HeLa cells. J Mol Biol 45:265–275

    Article  PubMed  CAS  Google Scholar 

  • Maden BEH, Corbett ME, Heeney PA, Pugh K, Ajuh PM (1995) Classical and novel approaches to the detection and localization of the numerous modified nucleotides in eukaryotic ribosomal RNA. Biochimie 72:22–29

    Article  Google Scholar 

  • Maxwell ES, Fournier ML (1995) The small nucleolar RNAs. Annu Rev Biochem 35:897–934

    Article  Google Scholar 

  • McCallum FS, Maden BEH (1985) Human 18S ribosomal RNA sequence inferred from DNA sequence: variations in 18S sequences and secondary modification patterns between vertebrates. Biochem J 232:725–733

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Morrissey JP, Tollervey D (1995) Birth of the snoRNPs: the evolution of RNase MRP and the eukaryotic pre-rRNA processing system. Trends Biochem Sci 20:78–82

    Article  PubMed  CAS  Google Scholar 

  • Mougey EB, Pape LK, Sollner-Webb B (1993) A U3 small nuclear ribonucleoprotein-requiring processing event in the 5′ external transcribed spacer ofXenopus precursor rRNA. Mol Cell Biol 13:5990–5998

    PubMed  CAS  Google Scholar 

  • Négre D, Weitzmann C, Ofengand J (1989a) In vitro methylation ofE. coli 16S ribosomal RNA. Proc Natl Acad Sci USA 86:4902–4906

    Article  PubMed  Google Scholar 

  • Négre D, Weitzman, C, Ofengand J (1989b) In vitro methylation ofEscherichia coli 16S RNA, 23S RNA, and 30S ribosomes by homologous cell-free extracts. In Jones PA, Clawson GA, Willis DB, Weisbach A (eds) Nucleic acid methylation. Willey-Liss. New York, pp 1–17

    Google Scholar 

  • Nicoloso M, Liang-Hu Q, Michot B, Bachellerie J-P (1996) Intron-encoded, antisense small nucleolar RNAs: the characterization of nine novel species points to their direct role as guides for the 2′-ribose methylation of rRNAs. J Mol Biol 260:178–195

    Article  PubMed  CAS  Google Scholar 

  • Ofengand J, Bakin A (1997) Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archaebacteria, mitochondria and chloroplasts. J Mol Biol 266:246–268

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Peculis BA, Steitz JA (1993) Disruption of U8 nucleolar snRNA inhibits 5.8S and 28S rRNA processing in theXenopus oocyte. Cell 73:1233–1245

    Article  PubMed  CAS  Google Scholar 

  • Raué HA, Klootwijk J, Musters W (1988) Evolutionary conservation of structure and function of high molecular weight ribosomal RNA. Prog Biophys Mol Biol 51:77–129

    Article  PubMed  Google Scholar 

  • Rimoldi OJ, Raghu B, Nag MK, Eliceiri GL (1993) Three new small nucleolar RNAs that are cross-linked in vivo to unique regions of pre-rRNA. Mol Cell Biol 13:4382–4390

    PubMed  CAS  Google Scholar 

  • Salim M, Maden BEH (1981) Nucleotide sequence ofXenopus laevis RNA inferred from gene sequence. Nature 291:205–208

    Article  PubMed  CAS  Google Scholar 

  • Samarsky DA, Balakin AG, Fournier MJ (1995) Characterization of three new snRNAs fromSaccharomyces cerevisiae: snr34, snR35 and snR36. Nucleic Acids Res 23:2548–2554

    PubMed  CAS  Google Scholar 

  • Savino R, Gerbi S (1990) In vivo disruption ofXenopus U3 snRNA affects ribosomal RNA processing. EMBO J 9:2299–2308

    PubMed  CAS  Google Scholar 

  • Schmitt ME, Clayton DA (1992) Yeast site-specific ribonucleo-protein endoribonuclease MRP contains an RNA component homologous to mammalian Rnase MRP RNA and essential for viability. Genes Dev 6:1975–1985

    PubMed  CAS  Google Scholar 

  • Schmitt ME, Clayton DA (1993) Nuclear RNase MRP is required for correct processing of pre-5.8S rRNA inSaccharomyces cerevisiae. Mol Cell Biol 13:7935–7941

    PubMed  CAS  Google Scholar 

  • Schmitt ME, Bennet JL, Dairaghi DJ, Clayton DA (1993) Secondary structure of RNase MRP RNA as predicted by phylogenetic comparison. FASEB J 7:208–213

    PubMed  CAS  Google Scholar 

  • Segal DM, Eichler DC (1991) A nucleolar 2′-0-methyltransferase: specificity and evidence for its role in the methylation of mouse 28S precursor ribosomal RNA. J Biol Chem 266:24385–24389

    PubMed  CAS  Google Scholar 

  • Swann PF, Peacock AC, Bunting S (1975) Carcinogenesis and cellular injury. The effect, of ethionine on ribonucleic acid synthesis in rat liver. Biochem J 150:335–344

    PubMed  CAS  Google Scholar 

  • Tollervey D (1987) A yeast small nuclear RNA is required for normal processing of pre-ribosomal RNA. EMBO J 6:4169–4175

    PubMed  CAS  Google Scholar 

  • Tollervey D, Guthrie C (1985) Deletion of a yeast small nuclear RNA gene impairs growth. EMBO J 4:3873–3878

    PubMed  CAS  Google Scholar 

  • 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 processing, pre-rRNA methylation and ribosome assembly. Cell 72:443–457

    Article  PubMed  CAS  Google Scholar 

  • Tyc K, Steitz JA (1989) U3, U8 and U13 comprise a new class of mammalian snRNAs localized in the cell nucleolus. EMBO J 8:3113–3119

    PubMed  CAS  Google Scholar 

  • Tycowski KT, Shu M-D, Steitz JA (1993) A small nucleolar RNA is processed from an intron of the human gene encoding ribosomal protein S3. Genes Dev 7:1176–1190

    PubMed  CAS  Google Scholar 

  • Tycowski KT, Shu M-D, Steitz JA (1994) Requirement for intron-encoded U22 small nucleolar RNA in 18S ribosomal RNA maturation. Science 266:1558–1561

    Article  PubMed  CAS  Google Scholar 

  • Van Knippenberg PH (1986) Structural and functional aspects of the N6, N6 dimethyladenosine in 16S ribosomal RNA. In: Hardersty B, Kramer G (eds) Structure, function and genetics of ribosomes. Springer, Berlin Heidelberg New York, pp 412–424

    Google Scholar 

  • Vaughan MH, Soeiro R, Warner JR, Darnell JE (1967) The effects of methionine deprivation on ribosome synthesis in HeLa cells. Proc Natl Acad Sci USA 58: 1527–1534

    Article  PubMed  CAS  Google Scholar 

  • Wise JA, Weiner AM (1980)Dictyostelium small nuclear RNA D2 is homologous to rat nucleolar RNA U3 and is encoded by a disperse multigene family. Cell 22:109–118

    Article  PubMed  CAS  Google Scholar 

  • Wolf SF, Schlesinger D (1977) Nuclear metabolism of ribosomal RNA in growing, methionine-limited and ethionine-treated HeLa cells. Biochemistry 16:2783–2791

    Article  PubMed  CAS  Google Scholar 

  • Zagorski J, Tollervey D, Fournier MJ (1988) Characterization of an SNR gene locus inSaccharomyces cerevisiae that specifies both dispensible and essential small nuclear RNAs. Mol Cell Biol 8:3282–3290

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Biological Sciences, University of Liverpool, Life Sciences Building, L69 7ZB, Liverpool, UK

    B. Edward H. Maden & John M. X. Hughes

Authors
  1. B. Edward H. Maden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John M. X. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maden, B.E.H., Hughes, J.M.X. Eukaryotic ribosomal RNA: the recent excitement in the nucleotide modification problem. Chromosoma 105, 391–400 (1997). https://doi.org/10.1007/BF02510475

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02510475

Keywords

Search

Navigation