Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1986 Jan 10;14(1):299–315. doi: 10.1093/nar/14.1.299

A dynamic programming algorithm for finding alternative RNA secondary structures.

A L Williams Jr, I Tinoco Jr
PMCID: PMC339410  PMID: 3003675

Abstract

Dynamic programming algorithms that predict RNA secondary structure by minimizing the free energy have had one important limitation. They were able to predict only one optimal structure. Given the uncertainties of the thermodynamic data and the effects of proteins and other environmental factors on structure, the optimal structure predicted by these methods may not have biological significance. We present a dynamic programming algorithm that can determine optimal and suboptimal secondary structures for an RNA. The power and utility of the method is demonstrated in the folding of the intervening sequence of the rRNA of Tetrahymena. By first identifying the major secondary structures corresponding to the lowest free energy minima, a secondary structure of possible biological significance is derived.

Full text

PDF
315

Images in this article

310Image
on p.310

Selected References

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

  1. Cech T. R., Tanner N. K., Tinoco I., Jr, Weir B. R., Zuker M., Perlman P. S. Secondary structure of the Tetrahymena ribosomal RNA intervening sequence: structural homology with fungal mitochondrial intervening sequences. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3903–3907. doi: 10.1073/pnas.80.13.3903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Comay E., Nussinov R., Comay O. An accelerated algorithm for calculating the secondary structure of single stranded RNAs. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):53–66. doi: 10.1093/nar/12.1part1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dumas J. P., Ninio J. Efficient algorithms for folding and comparing nucleic acid sequences. Nucleic Acids Res. 1982 Jan 11;10(1):197–206. doi: 10.1093/nar/10.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gold L., Pribnow D., Schneider T., Shinedling S., Singer B. S., Stormo G. Translational initiation in prokaryotes. Annu Rev Microbiol. 1981;35:365–403. doi: 10.1146/annurev.mi.35.100181.002053. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Jacobson A. B., Good L., Simonetti J., Zuker M. Some simple computational methods to improve the folding of large RNAs. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):45–52. doi: 10.1093/nar/12.1part1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kolter R., Yanofsky C. Attenuation in amino acid biosynthetic operons. Annu Rev Genet. 1982;16:113–134. doi: 10.1146/annurev.ge.16.120182.000553. [DOI] [PubMed] [Google Scholar]
  9. Martinez H. M. An RNA folding rule. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):323–334. doi: 10.1093/nar/12.1part1.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Noller H. F., Kop J., Wheaton V., Brosius J., Gutell R. R., Kopylov A. M., Dohme F., Herr W., Stahl D. A., Gupta R. Secondary structure model for 23S ribosomal RNA. Nucleic Acids Res. 1981 Nov 25;9(22):6167–6189. doi: 10.1093/nar/9.22.6167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nussinov R., Jacobson A. B. Fast algorithm for predicting the secondary structure of single-stranded RNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6309–6313. doi: 10.1073/pnas.77.11.6309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pipas J. M., McMahon J. E. Method for predicting RNA secondary structure. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2017–2021. doi: 10.1073/pnas.72.6.2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Price J. V., Kieft G. L., Kent J. R., Sievers E. L., Cech T. R. Sequence requirements for self-splicing of the Tetrahymena thermophila pre-ribosomal RNA. Nucleic Acids Res. 1985 Mar 25;13(6):1871–1889. doi: 10.1093/nar/13.6.1871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Quigley G. J., Gehrke L., Roth D. A., Auron P. E. Computer-aided nucleic acid secondary structure modeling incorporating enzymatic digestion data. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):347–366. doi: 10.1093/nar/12.1part1.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Studnicka G. M., Rahn G. M., Cummings I. W., Salser W. A. Computer method for predicting the secondary structure of single-stranded RNA. Nucleic Acids Res. 1978 Sep;5(9):3365–3387. doi: 10.1093/nar/5.9.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Uhlenbeck O. C., Borer P. N., Dengler B., Tinoco I., Jr Stability of RNA hairpin loops: A 6 -C m -U 6 . J Mol Biol. 1973 Feb 5;73(4):483–496. doi: 10.1016/0022-2836(73)90095-8. [DOI] [PubMed] [Google Scholar]
  22. Waring R. B., Scazzocchio C., Brown T. A., Davies R. W. Close relationship between certain nuclear and mitochondrial introns. Implications for the mechanism of RNA splicing. J Mol Biol. 1983 Jul 5;167(3):595–605. doi: 10.1016/s0022-2836(83)80100-4. [DOI] [PubMed] [Google Scholar]
  23. Waterman M. S. Sequence alignments in the neighborhood of the optimum with general application to dynamic programming. Proc Natl Acad Sci U S A. 1983 May;80(10):3123–3124. doi: 10.1073/pnas.80.10.3123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. von Gabain A., Belasco J. G., Schottel J. L., Chang A. C., Cohen S. N. Decay of mRNA in Escherichia coli: investigation of the fate of specific segments of transcripts. Proc Natl Acad Sci U S A. 1983 Feb;80(3):653–657. doi: 10.1073/pnas.80.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES