Journal of Molecular Evolution

, Volume 24, Issue 3, pp 236–251 | Cite as

The secondary structure of human 28S rRNA: The structure and evolution of a mosaic rRNA gene

  • Jerome L. Gorski
  • Iris L. Gonzalez
  • Roy D. Schmickel


We have determined the secondary structure of the human 28S rRNA molecule based on comparative analysis of available eukaryotic cytoplasmic and prokaryotic large-rRNA gene sequences. Examination of large-rRNA sequences of both distantly and closely related species has enabled us to derive a structure that accounts both for highly conserved sequence tracts and for previously unanalyzed variable-sequence tracts that account for the evolutionary differences in size among the large rRNAs.

Human 28S rRNA is composed of two different types of sequence tracts: conserved and variable. They differ in composition, degree of conservation, and evolution. The conserved regions demonstrate a striking constancy of size and sequence. We have confirmed that the conserved regions of large-rRNA molecules are capable of forming structures that are superimposable on one another. The variable regions contain the sequences responsible for the 83% increase in size of the human large-rRNA molecule over that ofEscherichia coli. Their locations in the gene are maintained during evolution. They are G+C rich and largely nonhomologous, contain simple repetitive sequences, appear to evolve by frequent recombinational events, and are capable of forming large, stable hairpins.

The secondary-structure model presented here is in close agreement with existing prokaryotic 23S rRNA secondary-structure models. The introduction of this model helps resolve differences between previously proposed prokaryotic and eukaryotic large-rRNA secondary-structure models.

Key words

28S rRNA RNA secondary structure Evolution Ribosome Translation 


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  1. Auron PE, Rindone WP, Vary CPH, Celentano JJ, Vournakis JN (1982) Computer-aided prediction of RNA secondary structures. Nucleic Acids Res 10:403–419PubMedGoogle Scholar
  2. Branlant C, Krol A, Machatt A, Pouyet J, Ebel JP, Edwards K, Kossel H (1981) Primary and secondary structures ofEscherichia coli MRE 600 23S ribosomal RNA. Comparison with models of secondary structure for maize chloroplast 23S rRNA and for large portions of mouse and human 16S mitochondrial rRNAs. Nucleic Acids Res 9:4303–4324PubMedGoogle Scholar
  3. Brimacombe R, Stiege W (1985) Structure and function of ribosomal RNA. Biochem J 229:1–17PubMedGoogle Scholar
  4. Brosius J, Dull TJ, Noller HF(1980) Complete nucleotide sequence of a 23S ribosomal RNA gene fromEscherichia coli. Proc Natl Acad Sci USA 77:201–204PubMedGoogle Scholar
  5. Chan YL, Olvera J, Wool IG (1983) The structure of rat 28S ribosomal ribonucleic acid inferred from the sequence of nucleotides in a gene. Nucleic Acids Res 11:7819–7831PubMedGoogle Scholar
  6. Clark CG, Tague BW, Ware VC, Gerbi SA (1984)Xenopus laevis 28S ribosomal RNA: a secondary structure model and its evolutionary and functional implications. Nucleic Acids Res 12:6197–6220PubMedGoogle Scholar
  7. DeBanzie JS, Steeg EW, Lis JT (1984) Update for users of the Cornell sequence analysis package. Nucleic Acids Res 12:619–625PubMedGoogle Scholar
  8. El-Baradi TTAL, Raue HA, DeRegt VCHF, Verbree EC, Planta RJ (1985) Yeast ribosomal protein L25 binds to an evolutionary conserved site on yeast 26S andE. coli 23S rRNA. EMBO J 4:2101–2107PubMedGoogle Scholar
  9. Erickson JM, Schmickel RD (1985) A molecular basis for discrete size variation in human ribosomal DNA. Am J Hum Genet 37:311–325PubMedGoogle Scholar
  10. Erickson JM, Rushford CL, Dorney DJ, Wilson GN, Schmickel RD (1981) Structure and variation of human ribosomal DNA: molecular analysis of cloned fragments. Gene 16:1–9PubMedGoogle Scholar
  11. Furlong JC, Maden BEH (1983) Patterns of major divergence between the internal transcribed spacers of ribosomal DNA inXenopus borealis andXenopus laevis, and of minimal divergence within ribosomal coding regions. EMBO J 2:443–448PubMedGoogle Scholar
  12. Furlong JC, Forbes J, Robertson M, Maden BEH (1983) The external transcribed spacer and preceding region ofXenopus borealis rDNA: a comparison with the corresponding region ofXenopus laevis rDNA. Nucleic Acids Res 11:8183–8196PubMedGoogle Scholar
  13. Glotz C, Zwieb C, Brimacombe R, Edwards K, Kessel H (1981) Secondary structure of the large subunit ribosomal RNA fromEscherichia coli, Zea mays chloroplast, and human and mouse mitochondrial ribosomes. Nucleic Acids Res 9:3287–3306PubMedGoogle Scholar
  14. Gonzalez IL, Gorski JL, Campen TJ, Dorney DJ, Erickson JM, Sylvester JE, Schmickel RD (1985) Variation among human 28S ribosomal RNA genes. Proc Natl Acad Sci USA 82:7666–7670PubMedGoogle Scholar
  15. Gourse RL, Thurlow DL, Gerbi SA, Zimmermann RA (1981) Specific binding of a prokaryotic ribosomal protein to a eukaryotic ribosomal RNA: implications for evolution and autoregulation. Proc Natl Acad Sci USA 78:2722–2726PubMedGoogle Scholar
  16. Grummt I, Roth E, Paule MR (1982) Ribosomal RNA transcription in vitro is species specific. Nature 296:173–174PubMedGoogle Scholar
  17. Hall LMC, Maden BE (1980) Nucleotide sequence through the 18S–28S intergene region of a vertebrate ribosomal transcription unit. Nucleic Acids Res 8:5993–6005PubMedGoogle Scholar
  18. Hassouna N, Michot B, Bachellerie JP (1984) The complete nucleotide sequence of mouse 28S rRNA gene. Implications for the process of size increase of the large subunit rRNA in higher eukaryotes. Nucleic Acids Res 12:3563–3583PubMedGoogle Scholar
  19. Henderson E, Oakes M, Clark MW, Lake JA, Matheson AT, Zillig W (1984) A new ribosome structure. Science 225:510–512PubMedGoogle Scholar
  20. Jain SK, Crampton J, Gonzalez IL, Schmickel RD, Drysdale JW (1985) Complementarity between ferritin H mRNA and 28S ribosomal RNA. Biochem Biophys Res Commun 131:863–868PubMedGoogle Scholar
  21. Jones TR, Parks CL, Spector DJ, Hyman RW (1985) Hybridization of herpes simplex virus DNA and human ribosomal DNA and RNA. Virology 144:384–397PubMedGoogle Scholar
  22. Kan LS, Chandrasegaran S, Pulford SM, Miller PS (1983) Detection of a guanine-adenine base pair in a decadeoxyribonucleotide by proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA 80:4263–4265PubMedGoogle Scholar
  23. Maly P, Brimacombe R (1983) Refined secondary structure models for the 16S and 23S ribosomal RNA ofEscherichia coli. Nucleic Acids Res 11:7263–7286PubMedGoogle Scholar
  24. Michot B, Bachellerie JP, Raynal F (1983) Structure of mouse rRNA precursors. Complete sequence and potential folding of the spacer regions between 18S and 28S rRNA. Nucleic Acids Res 11:3375–3396PubMedGoogle Scholar
  25. Michot B, Hassouna N, Bachellerie JP (1984) Secondary structure of mouse 28S rRNA and general model for the folding of the large rRNA in eukaryotes. Nucleic Acids Res 12:4259–4279PubMedGoogle Scholar
  26. Noller HF (1980) Structure and topography of ribosomal RNA. In: Chamblis G, Craven GR, Davies J, Davis K, Kahan L, Nomura M (eds) Ribosomes: structure, function and genetics. University Park Press, Baltimore, pp 3–22Google Scholar
  27. Noller HF (1984) Structure of ribosomal RNA. Annu Rev Biochem 53:119–162PubMedGoogle Scholar
  28. Noller HF, Kop JA, Wheaton V, Brosius J, Gutell RR, Kopylov AM, Dohme F, Herr W (1981) Secondary structure model for 23S ribosomal RNA. Nucleic Acids Res 9:6167–6189PubMedGoogle Scholar
  29. Otsuka T, Nomiyama H, Yoshida H, Kukita T, Kuhara S, Sakaki Y (1983) Complete nucleotide sequence of the 26S rRNA gene ofPhysarum polycephalum: its significance in gene evolution. Proc Natl Acad Sci USA 80:3163–3167PubMedGoogle Scholar
  30. Peattie DA, Douthwaite S, Garrett RA, Noller HF (1981) A “bulged” double helix in a RNA-protein contact site. Proc Natl Acad Sci USA 78:7331–7335PubMedGoogle Scholar
  31. Schibler U, Wyler T, Hagenbuchle O (1977) Changes in size and secondary structure of the ribosomal transcription unit during vertebrate evolution. J Mol Biol 94:503–517Google Scholar
  32. Sellers PH (1974) Theory and computation of evolutionary distances. SIAM J Appl Math 26:787–793Google Scholar
  33. Smith GP (1976) Evolution of repeated DNA sequences by unequal crossover. Science 191:528–535PubMedGoogle Scholar
  34. Smith TF, Waterman MS (1981) Identification of common molecular sequences. J Mol Biol 147:195–197PubMedGoogle Scholar
  35. Stiege W, Zwieb C, Brimacombe R (1982) Precise localization of three intra-RNA crosslinks in 23S RNA, and one in 5S RNA, induced by treatment ofEscherichia coli 50S ribosomal subunits with bis-(2-chloroethyl)-methylamine. Nucleic Acids Res 10:7211–7229PubMedGoogle Scholar
  36. Stiege W, Glotz C, Brimacombe R (1983) Localization of a series of intra-RNA crosslinks in the secondary and tertiary structure of 23S RNA, induced by ultraviolet irradiation ofEscherichia coli 50S ribosomal subunits. Nucleic Acids Res 11:1687–1706PubMedGoogle Scholar
  37. Subrahmanyam CS, Cassidy B, Busch H, Rothblum LI (1982) Nucleotide sequence of the region between the 18S rRNA sequence and the 28S rRNA sequence of rat ribosomal DNA. Nucleic Acids Res 10:3667–3680PubMedGoogle Scholar
  38. Turner S, Noller HF (1983) Identification of sites of 4′-(hydroxymethyl)-4,5′,8-trimethylpsoralen cross-linking inEscherichia coli 23S ribosomal ribonucleic acid. Biochemistry 22:4159–4164PubMedGoogle Scholar
  39. Vaughn JC, Sperbeck SJ, Ramsey WJ, Lawrence CB (1984) A universal model for the secondary structure of 5.8S ribosomal RNA molecules, their contact sites with 28S ribosomal RNAs, and their prokaryotic equivalent. Nucleic Acids Res 12:7479–7502PubMedGoogle Scholar
  40. Veldman GM, Klootwijk J, deRegt VCHF, Planta RJ, Branlant C, Krol A, Ebel JP (1981) The primary and secondary structure of yeast 26S rRNA. Nucleic Acids Res 9:6935–6952PubMedGoogle Scholar
  41. Vester B, Garrett RA (1984) Structure of a protein L 23 RNA complex located at the A-site domain of the ribosomal peptidyl transferase center. J Mol Biol179:431–452PubMedGoogle Scholar
  42. Walker TA, Pace NR (1983) 5.8S ribosomal RNA. Cell 33:320–322PubMedGoogle Scholar
  43. Ware VC, Tague BW, Clark CG, Gourse RL, Brand RC, Gerbi SA (1983) Sequence analysis of 28S ribosomal DNA from the amphibianXenopus laevis. Nucleic Acids Res 11:7795–7817PubMedGoogle Scholar
  44. Woese CR (1980) Just so stories and Rube Goldberg machines: speculations on the origin of the protein synthetic machinery. In: Chamblis G, Craven GR, Davies J, Davis K, Kahan L, Nomura M (eds) Ribosomes: structure, function and genetics. University Park Press, Baltimore, pp 357–373Google Scholar
  45. Woese CR, Gutell R, Gupta R, Noller HF (1983) Detailed analysis of the higher-order structure of 16S-like ribosomal ribonucleic acids. Microbiol Rev 47:621–669PubMedGoogle Scholar
  46. Zaug AJ, Cech TR (1986) The intervening sequence ofTetrahymena is an enzyme. Science 231:470–476PubMedGoogle Scholar
  47. Zimmermann RA (1979) Interactions among protein and RNA components of the ribosome. In: Chamblis G, Craven GR, Davies J, Davis K, Kahan L, Nomura M (eds) Ribosomes: structure, function and genetics. University Park Press, Baltimore, pp 135–169Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1987

Authors and Affiliations

  • Jerome L. Gorski
    • 1
  • Iris L. Gonzalez
    • 1
  • Roy D. Schmickel
    • 1
  1. 1.Department of Human GeneticsUniversity of PennsylvaniaPhiladelphiaUSA

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