Abstract
Sophisticated regulatory structures appear within highly-constrained coding regions of genes. We study the extent to which such structures can be constructed. Can such stem loops appear essentially anywhere within coding regions, or is the potential restricted to rare amino acid sequences? While predicting secondary structures of an RNA sequence is an extensively studied problem in computational biology, the inverse problem, designing sequences based on a known structure is also important. We work on a particular version of the inverse RNA folding problem, where our goal is to achieve a targeted energy level. For a particular RNA structure, we design sequences with the maximum and minimum folding energy while maintaining desired codon distribution. Our major contributions in work is to optimize RNA secondary structure under codon constraints via fast estimation of folding energies following local modification.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Zuker, M., Mathews, D.H., Turner, D.H.: Algorithms and thermodynamics for rna secondary structure prediction (1999)
Jaeger, J., Turner, D.H., Zuker, M.: Improved predictions of secondary structures for rna. Proc. Natl. Acad. Sci. USA 86, 7706–7710 (1989)
Tinoco, I.J., Borer, P., Dengler, B., Levin, M., Uhlenbeck, O., Crothers, D., Bralla, J.: Improved estimation of secondary structure in ribonucleic acids. Nat. New Biol. 246, 40–41 (1973)
Hofacker, I.L., Fontana, W., Stadler, P.F., Bonhoeffer, L.S.: Fast folding and comparison of rna secondary structures. Monatshefte fur Chemie 125, 167–188 (1994)
Cohen, B., Skiena, S.: Natural selection and algorithmic design of mRNA. J. Computational Biology 10, 419–432 (2003)
Cohen, B., Skiena, S.: Optimizing rna secondary structure over all possible encodings of a given protein. In: RECOMB (2000)
Kudla, G., Murray, A., Tollervey, D., Plotkin, J.: Coding-sequence determinants of gene expression in escherichia coli. Science 324, 255–258 (2009)
Plotkin, J., Kudla, G.: Synonymous but not the same: the causes and consequences of codon bias. Nature Reviews Genetics 12, 32–42 (2011)
Tuller, T., Waldman, Y.Y., Kupiec, M., Ruppin, E.: Translation efficiency is determined by both codon bias and folding energy. Natl. Acad. Sci. USA
Sitaraman, V., Hearing, P., Ward, C., Gnatenko, D., Wimmer, E., Mueller, S., Skiena, S., Bahou, W.: Computationally designed adeno-associated virus (aav) rep 78 is efficiently maintained within an adenovirus vector. Proc. National Academy of Sciences 108, 14294–14299 (2011)
Mueller, S., Coleman, R., Papamichail, D., Ward, C., Nimnual, A., Futcher, B., Skiena, S., Wimmer, E.: Live attenuated influenza vaccines by computer-aided rational design. Nature Biotechnology 28 (2010)
Coleman, J., Papamichial, D., Futcher, B., Skiena, S., Mueller, S., Wimmer, E.: Virus attenuation by genome-scale changes in codon-pair bias. Science 320, 1784–1787 (2008)
Zuker, M.: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406–3415 (2003)
Mathews, D., Sabina, J., Zuker, M., Turner, D.: Expanded sequence dependence of thermodynamic parameters improves prediction of rna secondary structure. J. Mol. Biol. 288, 911–940 (1999)
Zuker, M., Stiegler, P.: Optimal computer folding of large rna sequences using thermodynamics and auxiliary information. Nucleic Acids Res., 133–148 (1981)
McCaskill, J.: The equilibrium partition function and base pair binding probabilities for rna secondary structure. Biopolymers 29, 1105–1119 (1990)
Wuchty, S., Fontana, W., L.H. I., Schuster, P.: Complete suboptimal folding of rna and the stability of secondary structures. Biopolymers 49, 145–165 (1999)
Shapiro, B.A., Zhang, K.: Comparing multiple rna secondary structures using tree comparisons. Comput. Appl. Biosci. 6, 309–318 (1990)
Hofacker, I.L.: The rules of the evolutionary game for rna: A statistical characterization of the sequence to structure mapping in rna. PhD thesis
Dromi, N., Avihoo, A., Barash, D.: Reconstruction of natural rna sequences from rna shape, thermodynamic stability, mutational robustness, and linguistic complexity by evolutionary computation. Biomol. Struct. Dyn. 26, 147–162 (2008)
Dehiyat, B.I., Mayo, S.L.: De novo protein design: Fully automated sequence selection. Science 278, 82–87 (1997)
Busch, A., Backofen, R.: Info-rna: a server for fast inverse rna folding satisfying sequence constraints. Nucleic Acids Res. (2007)
Avihoo, A., Churkin, A., Barash, D.: Rnaexinv: An extended inverse rna folding from shape and physical attributes to sequences. BMC Bioinformatics
Durbin, R., Eddy, S., Krogh, A., Mitchison, G.: Biological sequence analysis: Probabilistic models of proteins and nucleic acids. Cambridge University Press (1998)
Knudsen, B., Hein, J.: Rna secondary structure prediction using stochastic context-free grammars and evolutionary history. Bioinformatics 15, 446–454 (1999)
Dowell, R., Eddy, S.: Evaluation of several lightweight stochastic context-free grammars for rna secondary structure prediction. BMC Bioinformatics 5 (2004)
Do, C.B., Woods, D.A., Batzoglou, S.: Contrafold: Rna secondary structure prediction without physics-based models. Bioinformatics 22, 90–98 (2006)
Andronescu, M., Condon, A., Hoos, H.H., Mathews, D.H., Murphy, K.P.: Efficient parameter estimation for rna secondary structure prediction. Bioinformatics 23 (2007)
Andronescu, M.: Computational approaches for rna energy parameter estimation. PhD thesis, University of British Columbia, Vancouver, Canada
Zakov, S., Goldberg, Y., Elhadad, M., Ziv-Ukelson, M.: Rich Parameterization Improves RNA Structure Prediction. In: Bafna, V., Sahinalp, S.C. (eds.) RECOMB 2011. LNCS, vol. 6577, pp. 546–562. Springer, Heidelberg (2011)
Doshi, K.J., Cannone, J.J., Cobaugh, C.W., Gutell, R.R.: Evaluation of the suitability of free-energy minimization using nearest-neighbor energy parameters for rna secondary structure prediction. BMC Bioinformatics 5, 105 (2004)
Metropolis, N., Rosenbluth, A.W., Rosenbluth, M.N., Teller, A.H., Teller, E.: Equation of state by fast computing machines. The Journal of Chemical Physics 21, 1087–1092 (1953)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Yeasmin, R., Skiena, S. (2012). Designing RNA Secondary Structures in Coding Regions. In: Bleris, L., Măndoiu, I., Schwartz, R., Wang, J. (eds) Bioinformatics Research and Applications. ISBRA 2012. Lecture Notes in Computer Science(), vol 7292. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30191-9_28
Download citation
DOI: https://doi.org/10.1007/978-3-642-30191-9_28
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-30190-2
Online ISBN: 978-3-642-30191-9
eBook Packages: Computer ScienceComputer Science (R0)