Journal of Molecular Evolution

, Volume 21, Issue 4, pp 323–333 | Cite as

U1 snRNA: The evolution of its primary and secondary structure

  • P. Hogeweg
  • D. A. M. Konings


In this paper we first show that the primary structure of U1 snRNA is homologous to that of tandem repeated pre-tRNA. Two sets of polymerase III promoter sites (the a and b boxes) are clearly recognisable at the appropriate positions in U1, although neither is functional; these sites occur in a degenerate form and their transcription is initiated by polymerase II. Moreover, several of the conserved subsequences of tRNAs that are not associated with transcription initiation (and supposedly are conserved because of their role in translation) are conserved in U1 as well, one of them being the pattern Py-Py-anticodon-Pu-Pu (for both anticodons of tandem tRNA).

Second, we show that the secondary structure of U1 is apparently formed after fixation of the ‘B-hairpin loop’ by one of the associated proteins. If and only if this hairpin loop is fixed, a consensus secondary structure is produced by the minimisation-of-free-energy technique. Moreover, we show that this B-hairpin loop has been destabilised relatively recently in evolutionary time by deletions (e.g., in the polymerase III box). If we reinsert the deleted bases, the so constructed hypothetical “ancestral” molecule folds into the consensus secondary structure by unconstrained energy minimisation (i.e., without fixation of the B-loop).

Some features of the secondary structure of tandem repeated pre-tRNA are conserved in U1, but the overall structure has changed dramatically. Like tRNA, U1 has a cloverleaf-like structure, but its overall size has doubled. By comparing their secondary structures and by alignment of the sequences, we trace the local events associated with the global change in secondary structure (and apparently in the function of the molecule).

Finally, we discuss our results from the perspective of informatic prerequisites for heterarchical multilevel evolution.

Key words

U1 snRNA Tandem repeated pre-tRNA Constrained minimal-energy folding Homology assessment Multilevel evolution 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Altmann S (1975) Biosynthesis of transfer RNA inEscherichia coli. Cell 4:21–29CrossRefPubMedGoogle Scholar
  2. Auron PE, Rindone WP, Vary CPH, Celentano JJ, Vournakis JN (1982) Computer aided prediction of RNA secondary structure. Nucleic Acids Res 10:403–419PubMedGoogle Scholar
  3. Bhat RA, Metz B, Thimmappaya B (1983) Organisation of noncontiguous coding components of adenovirus VAI RNA gene is strikingly similar to that of eukaryotic tRNA genes. Mol Cell Biol 3:1996–2005PubMedGoogle Scholar
  4. Bralant C, Krol A, Ebel JP (1981) The conformation of chicken, rat and human U1a RNA's in solution. Nucleic Acids Res 9:841–858PubMedGoogle Scholar
  5. Ciliberto G, Rangel G, Costanzo F, Dente L, Cortese R (1983) Common and interchangeable elements in the promoters of genes transcribed by polymerase III. Cell 32:725–733CrossRefPubMedGoogle Scholar
  6. Dayhoff MO, Schwartz RM, Chen HR, Hunt LT, Barker, WC, Orcutt BC (1981) Nucleic acid sequence database, vol 1. National Biomedical Research Foundation, Washington DCGoogle Scholar
  7. Doolittle WF (1978) Genes in pieces: Were they ever together? Nature 272:581–582PubMedGoogle Scholar
  8. Eigen M, Schuster P (1977) The hypercycle I. Naturwissenschaften 64:541–565CrossRefPubMedGoogle Scholar
  9. Eigen M, Schuster P (1978) The hypercycle II. Naturwissenschaften 65:7–41CrossRefGoogle Scholar
  10. Eigen M, Schuster P (1979) The hypercycle III. Naturwissenschaften 65:341–369CrossRefGoogle Scholar
  11. Eigen M, Winkler-Oswatitsch R (1981) Transfer-RNA: the early adaptor. Naturwissenschaften 68:217–292CrossRefPubMedGoogle Scholar
  12. Fuhrman SA, Engelke DR, Geidushek EP (1984) HeLa cell RNA polymerase III transcription factors. Biol Chem 259:1934–1943Google Scholar
  13. Galli G, Hofstetter, H, Birnstiel M (1981) Two conserved sequence blocks within eukaryotic tRNA genes are major promoter elements. Nature 294:626–631CrossRefPubMedGoogle Scholar
  14. Garett RA, Douthwaite S, Noller HF (1981) Structure and role of 5S RNA-protein complexes in protein biosyntheses. TIBS 6:137–139Google Scholar
  15. Hofstetter H, Kressman A, Birnstiel M (1981) A split promoter for eukaryotic tRNA gene. Cell 25:573–584CrossRefGoogle Scholar
  16. Hogeweg P, Hesper B (1984a) Energy directed folding of RNA sequences. Nucleic Acids Res 12:67–74PubMedGoogle Scholar
  17. Hogeweg P, Hesper B (1984b) The alignment of sets of sequences and the construction of phyletic trees: an integrated method. J Mol Evol 20:175–186PubMedGoogle Scholar
  18. Lund E, Dahlberg JE (1984) True genes for human U1 small nuclear RNA. Biol Chem 259:2013–2021Google Scholar
  19. Marzluff WF, Brown DT, Lobo S, Wang SS (1983) Isolation and characterisation of two linked mouse U1-b small nuclear RNA genes. Nucleic Acids Res 11:6255–6270PubMedGoogle Scholar
  20. Mount NSM, Steitz JA (1981) Sequence of U1 RNA fromDrosophila melanogaster: implications for U1 secondary structure and possible involvement in splicing. Nucleic Acids Res 9:6351–6368PubMedGoogle Scholar
  21. Murphy MH, Baralle FE (1983) Directed, semisynthetic point mutational analysis of an RNA polymerase III. Nucleic Acids Res 11:7695–7700PubMedGoogle Scholar
  22. Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in amino acid sequences of two proteins. J Mol Biol 48:443–453CrossRefPubMedGoogle Scholar
  23. Nussinov R, Jacobson AB (1980) Fast algorithm for predicting the secondary structure of single-stranded RNA. Proc Natl Acad Sci USA 77:6309–6313PubMedGoogle Scholar
  24. Nussinov R, Tinoco I (1981) Sequential folding of a messenger RNA molecule. J Mol Biol 151:519–533CrossRefPubMedGoogle Scholar
  25. Nussinov R, Pieczenik G, Griggs JR, Kleitman DJ (1978) Algorithms for loop matchings. SIAM J Appl Math 35:68–82CrossRefGoogle Scholar
  26. Nussinov R, Tinoco I, Jacobson AB (1982) Small changes in free energy assignments for unpaired bases do not affect predicted secondary structures in single stranded RNA. Nucleic Acids Res 10:341–349PubMedGoogle Scholar
  27. Pipas JM, McMahon JE (1975) Method for predicting RNA secondary structure. Proc Natl Acad Sci USA 72:2017–2021PubMedGoogle Scholar
  28. Queen CL, Korn LJ (1980) Computer analysis of nucleic acids and proteins. Methods Enzymol 65:595–609PubMedGoogle Scholar
  29. Rohan RM, Ketner G (1983) Point mutations in the regulatory region of the human adenovirus Va1 gene. Biol Chem 258:11576–11581Google Scholar
  30. Salser W (1977) Globin mRNA sequences: analysis of base pairing and evolutionary implications. Cold Spring Harbor Symp Quant Biol 42:985–1102Google Scholar
  31. Sellars PH (1974) On the theory of the computation of evolutionary distances. SIAM J Appl Math 26:787–793CrossRefGoogle Scholar
  32. Smith TF, Waterman MS, Fitch WM (1981) Comparative biosequence metrics. J Mol Evol 18:38–46CrossRefPubMedGoogle Scholar
  33. Studnicka GM, Rahn GM, Cummings IW, Salser WA (1978) Computer method for predicting the secondary structure of single stranded RNA. Nucleic Acids Res 5:3365–3387PubMedGoogle Scholar
  34. Waterman MS, Smith TF, Beyer WA (1976) Some biological sequence metrics. Adv Math 20:267–287CrossRefGoogle Scholar
  35. Woese CR, Luersen CDP, Fox GE (1976) Sequence characterisation of 5S ribosomal RNA from eight Gram-positive prokaryotes. J Mol Evol 8:143–153CrossRefPubMedGoogle Scholar
  36. Zucker M, Striegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res 9:133–148PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • P. Hogeweg
    • 1
  • D. A. M. Konings
    • 1
  1. 1.BIOINFORMATICAUtrechtThe Netherlands

Personalised recommendations