Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Oct;86(20):7706–7710. doi: 10.1073/pnas.86.20.7706

Improved predictions of secondary structures for RNA.

J A Jaeger 1, D H Turner 1, M Zuker 1
PMCID: PMC298139  PMID: 2479010

Abstract

The accuracy of computer predictions of RNA secondary structure from sequence data and free energy parameters has been increased to roughly 70%. Performance is judged by comparison with structures known from phylogenetic analysis. The algorithm also generates suboptimal structures. On average, the best structure within 10% of the lowest free energy contains roughly 90% of phylogenetically known helixes. The algorithm does not include tertiary interactions or pseudoknots and employs a crude model for single-stranded regions. The only favorable interactions are base pairing and stacking of terminal unpaired nucleotides at the ends of helixes. The excellent performance is consistent with these interactions being the primary interactions determining RNA secondary structure.

Full text

PDF
7710

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borer P. N., Dengler B., Tinoco I., Jr, Uhlenbeck O. C. Stability of ribonucleic acid double-stranded helices. J Mol Biol. 1974 Jul 15;86(4):843–853. doi: 10.1016/0022-2836(74)90357-x. [DOI] [PubMed] [Google Scholar]
  2. Burke J. M., Belfort M., Cech T. R., Davies R. W., Schweyen R. J., Shub D. A., Szostak J. W., Tabak H. F. Structural conventions for group I introns. Nucleic Acids Res. 1987 Sep 25;15(18):7217–7221. doi: 10.1093/nar/15.18.7217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coutts S. M., Gangloff J., Dirheimer G. Conformational transitions in tRNA Asp (brewer's yeast). Thermodynamic, kinetic, and enzymatic measurements on oligonucleotide fragments and the intact molecule. Biochemistry. 1974 Sep 10;13(19):3938–3948. doi: 10.1021/bi00716a019. [DOI] [PubMed] [Google Scholar]
  4. Fink T. R., Crothers D. M. Free energy of imperfect nucleic acid helices. I. The bulge defect. J Mol Biol. 1972 Apr 28;66(1):1–12. doi: 10.1016/s0022-2836(72)80002-0. [DOI] [PubMed] [Google Scholar]
  5. Freier S. M., Alkema D., Sinclair A., Neilson T., Turner D. H. Contributions of dangling end stacking and terminal base-pair formation to the stabilities of XGGCCp, XCCGGp, XGGCCYp, and XCCGGYp helixes. Biochemistry. 1985 Aug 13;24(17):4533–4539. doi: 10.1021/bi00338a008. [DOI] [PubMed] [Google Scholar]
  6. Freier S. M., Kierzek R., Caruthers M. H., Neilson T., Turner D. H. Free energy contributions of G.U and other terminal mismatches to helix stability. Biochemistry. 1986 Jun 3;25(11):3209–3213. doi: 10.1021/bi00359a019. [DOI] [PubMed] [Google Scholar]
  7. Freier S. M., Kierzek R., Jaeger J. A., Sugimoto N., Caruthers M. H., Neilson T., Turner D. H. Improved free-energy parameters for predictions of RNA duplex stability. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9373–9377. doi: 10.1073/pnas.83.24.9373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Freier S. M., Sugimoto N., Sinclair A., Alkema D., Neilson T., Kierzek R., Caruthers M. H., Turner D. H. Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids. Biochemistry. 1986 Jun 3;25(11):3214–3219. doi: 10.1021/bi00359a020. [DOI] [PubMed] [Google Scholar]
  9. Gewirth D. T., Moore P. B. Exploration of the L18 binding site on 5S RNA by deletion mutagenesis. Nucleic Acids Res. 1988 Nov 25;16(22):10717–10732. doi: 10.1093/nar/16.22.10717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. 3. Small internal loops resulting from mismatches. J Mol Biol. 1973 Aug 5;78(2):301–319. doi: 10.1016/0022-2836(73)90118-6. [DOI] [PubMed] [Google Scholar]
  11. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. II. Small hairpin loops. J Mol Biol. 1973 Feb 5;73(4):497–511. doi: 10.1016/0022-2836(73)90096-x. [DOI] [PubMed] [Google Scholar]
  12. Groebe D. R., Uhlenbeck O. C. Characterization of RNA hairpin loop stability. Nucleic Acids Res. 1988 Dec 23;16(24):11725–11735. doi: 10.1093/nar/16.24.11725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gutell R. R., Weiser B., Woese C. R., Noller H. F. Comparative anatomy of 16-S-like ribosomal RNA. Prog Nucleic Acid Res Mol Biol. 1985;32:155–216. doi: 10.1016/s0079-6603(08)60348-7. [DOI] [PubMed] [Google Scholar]
  14. Kierzek R., Caruthers M. H., Longfellow C. E., Swinton D., Turner D. H., Freier S. M. Polymer-supported RNA synthesis and its application to test the nearest-neighbor model for duplex stability. Biochemistry. 1986 Dec 2;25(24):7840–7846. doi: 10.1021/bi00372a009. [DOI] [PubMed] [Google Scholar]
  15. Michel F., Cummings D. J. Analysis of class I introns in a mitochondrial plasmid associated with senescence of Podospora anserina reveals extraordinary resemblance to the Tetrahymena ribosomal intron. Curr Genet. 1985;10(1):69–79. doi: 10.1007/BF00418495. [DOI] [PubMed] [Google Scholar]
  16. Michel F., Dujon B. Conservation of RNA secondary structures in two intron families including mitochondrial-, chloroplast- and nuclear-encoded members. EMBO J. 1983;2(1):33–38. doi: 10.1002/j.1460-2075.1983.tb01376.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Michel F., Jacquier A., Dujon B. Comparison of fungal mitochondrial introns reveals extensive homologies in RNA secondary structure. Biochimie. 1982 Oct;64(10):867–881. doi: 10.1016/s0300-9084(82)80349-0. [DOI] [PubMed] [Google Scholar]
  18. Milligan J. F., Groebe D. R., Witherell G. W., Uhlenbeck O. C. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res. 1987 Nov 11;15(21):8783–8798. doi: 10.1093/nar/15.21.8783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moazed D., Stern S., Noller H. F. Rapid chemical probing of conformation in 16 S ribosomal RNA and 30 S ribosomal subunits using primer extension. J Mol Biol. 1986 Feb 5;187(3):399–416. doi: 10.1016/0022-2836(86)90441-9. [DOI] [PubMed] [Google Scholar]
  20. Moore P. B. On the modus operandi of the ribosome. Cold Spring Harb Symp Quant Biol. 1987;52:721–728. doi: 10.1101/sqb.1987.052.01.081. [DOI] [PubMed] [Google Scholar]
  21. Papanicolaou C., Gouy M., Ninio J. An energy model that predicts the correct folding of both the tRNA and the 5S RNA molecules. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):31–44. doi: 10.1093/nar/12.1part1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pleij C. W., Rietveld K., Bosch L. A new principle of RNA folding based on pseudoknotting. Nucleic Acids Res. 1985 Mar 11;13(5):1717–1731. doi: 10.1093/nar/13.5.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Riesner D., Maass G., Thiebe R., Philippsen P., Zachau H. G. The conformational transitions in yeast tRNAPhe as studied with tRNAPhe fragments. Eur J Biochem. 1973 Jul 2;36(1):76–88. doi: 10.1111/j.1432-1033.1973.tb02887.x. [DOI] [PubMed] [Google Scholar]
  24. Romby P., Westhof E., Toukifimpa R., Mache R., Ebel J. P., Ehresmann C., Ehresmann B. Higher order structure of chloroplastic 5S ribosomal RNA from spinach. Biochemistry. 1988 Jun 28;27(13):4721–4730. doi: 10.1021/bi00413a021. [DOI] [PubMed] [Google Scholar]
  25. Salser W. Globin mRNA sequences: analysis of base pairing and evolutionary implications. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):985–1002. doi: 10.1101/sqb.1978.042.01.099. [DOI] [PubMed] [Google Scholar]
  26. Shub D. A., Gott J. M., Xu M. Q., Lang B. F., Michel F., Tomaschewski J., Pedersen-Lane J., Belfort M. Structural conservation among three homologous introns of bacteriophage T4 and the group I introns of eukaryotes. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1151–1155. doi: 10.1073/pnas.85.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sprinzl M., Hartmann T., Meissner F., Moll J., Vorderwülbecke T. Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 1987;15 (Suppl):r53–188. doi: 10.1093/nar/15.suppl.r53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sugimoto N., Kierzek R., Turner D. H. Kinetics for reaction of a circularized intervening sequence with CU, UCU, CUCU, and CUCUCU: mechanistic implications from the dependence on temperature and on oligomer and Mg2+ concentrations. Biochemistry. 1988 Aug 23;27(17):6384–6392. doi: 10.1021/bi00417a029. [DOI] [PubMed] [Google Scholar]
  29. Tinoco I., Jr, Borer P. N., Dengler B., Levin M. D., Uhlenbeck O. C., Crothers D. M., Bralla J. Improved estimation of secondary structure in ribonucleic acids. Nat New Biol. 1973 Nov 14;246(150):40–41. doi: 10.1038/newbio246040a0. [DOI] [PubMed] [Google Scholar]
  30. Tinoco I., Jr, Uhlenbeck O. C., Levine M. D. Estimation of secondary structure in ribonucleic acids. Nature. 1971 Apr 9;230(5293):362–367. doi: 10.1038/230362a0. [DOI] [PubMed] [Google Scholar]
  31. Tuerk C., Gauss P., Thermes C., Groebe D. R., Gayle M., Guild N., Stormo G., d'Aubenton-Carafa Y., Uhlenbeck O. C., Tinoco I., Jr CUUCGG hairpins: extraordinarily stable RNA secondary structures associated with various biochemical processes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1364–1368. doi: 10.1073/pnas.85.5.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Turner D. H., Sugimoto N., Freier S. M. RNA structure prediction. Annu Rev Biophys Biophys Chem. 1988;17:167–192. doi: 10.1146/annurev.bb.17.060188.001123. [DOI] [PubMed] [Google Scholar]
  33. Uhlenbeck O. C., Martin F. H., Doty P. Self-complementary oligoribonucleotides: effects of helix defects and guanylic acid-cytidylic acid base pairs. J Mol Biol. 1971 Apr 28;57(2):217–229. doi: 10.1016/0022-2836(71)90342-1. [DOI] [PubMed] [Google Scholar]
  34. Waring R. B., Davies R. W. Assessment of a model for intron RNA secondary structure relevant to RNA self-splicing--a review. Gene. 1984 Jun;28(3):277–291. doi: 10.1016/0378-1119(84)90145-8. [DOI] [PubMed] [Google Scholar]
  35. Williams A. L., Jr, Tinoco I., Jr A dynamic programming algorithm for finding alternative RNA secondary structures. Nucleic Acids Res. 1986 Jan 10;14(1):299–315. doi: 10.1093/nar/14.1.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Williams A. P., Longfellow C. E., Freier S. M., Kierzek R., Turner D. H. Laser temperature-jump, spectroscopic, and thermodynamic study of salt effects on duplex formation by dGCATGC. Biochemistry. 1989 May 16;28(10):4283–4291. doi: 10.1021/bi00436a025. [DOI] [PubMed] [Google Scholar]
  37. Woese C. R. Bacterial evolution. Microbiol Rev. 1987 Jun;51(2):221–271. doi: 10.1128/mr.51.2.221-271.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wolters J., Erdmann V. A. Compilation of 5S rRNA and 5S rRNA gene sequences. Nucleic Acids Res. 1988;16 (Suppl):r1–70. doi: 10.1093/nar/16.suppl.r1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yuan R. C., Steitz J. A., Moore P. B., Crothers D. M. The 3' terminus of 16S rRNA: secondary structure and interaction with ribosomal protein S1. Nucleic Acids Res. 1979 Dec 20;7(8):2399–2418. doi: 10.1093/nar/7.8.2399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zuker M. On finding all suboptimal foldings of an RNA molecule. Science. 1989 Apr 7;244(4900):48–52. doi: 10.1126/science.2468181. [DOI] [PubMed] [Google Scholar]
  41. Zuker M., Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148. doi: 10.1093/nar/9.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES