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Structural Analysis of Single-Point Mutations Given an RNA Sequence: A Case Study with RNAMute
EURASIP Journal on Advances in Signal Processing volume 2006, Article number: 056246 (2006)
We introduce here for the first time the RNAMute package, a pattern-recognition-based utility to perform mutational analysis and detect vulnerable spots within an RNA sequence that affect structure. Mutations in these spots may lead to a structural change that directly relates to a change in functionality. Previously, the concept was tried on RNA genetic control elements called "riboswitches" and other known RNA switches, without an organized utility that analyzes all single-point mutations and can be further expanded. The RNAMute package allows a comprehensive categorization, given an RNA sequence that has functional relevance, by exploring the patterns of all single-point mutants. For illustration, we apply the RNAMute package on an RNA transcript for which individual point mutations were shown experimentally to inactivate spectinomycin resistance in Escherichia coli. Functional analysis of mutations on this case study was performed experimentally by creating a library of point mutations using PCR and screening to locate those mutations. With the availability of RNAMute, preanalysis can be performed computationally before conducting an experiment.
Waterman MS, Smith TF: RNA secondary structure: a complete mathematical analysis. Mathematical Biosciences 1978, 42(3–4):257–266. 10.1016/0025-5564(78)90099-8
Zuker M: Calculating nucleic acid secondary structure. Current Opinion in Structural Biology 2000, 10(3):303–310. 10.1016/S0959-440X(00)00088-9
Nussinov R, Jacobson AB: Fast algorithm for predicting the secondary structure of single-stranded RNA. Proceedings of the National Academy of Sciences 1980, 77(11):6309–6313. 10.1073/pnas.77.11.6309
Zuker M, Stiegler P: Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Research 1981, 9(1):133–148. 10.1093/nar/9.1.133
Zuker M, Sankoff D: RNA secondary structures and their prediction. Bulletin of Mathematical Biology 1984, 46(4):591–621.
Zuker M: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Research 2003, 31(13):3406–3415. 10.1093/nar/gkg595
Hofacker IL: Vienna RNA secondary structure server. Nucleic Acids Research 2003, 31(13):3429–3431. 10.1093/nar/gkg599
Mathews DH, Sabina J, Zuker M, Turner DH: Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. Journal of Molecular Biology 1999, 288(5):911–940. 10.1006/jmbi.1999.2700
Gutell RR, Lee JC, Cannone JJ: The accuracy of ribosomal RNA comparative structure models. Current Opinion in Structural Biology 2002, 12(3):301–310. 10.1016/S0959-440X(02)00339-1
Zimmerman JM, Maher LJ III: In vivo selection of spectinomycin-binding RNAs. Nucleic Acids Research 2002, 30(24):5425–5435. 10.1093/nar/gkf687
Barash D, Comaniciu D: A common viewpoint on broad kernel filtering and nonlinear diffusion. Proceedings of the 4th International Conference on Scale-Space Theories in Computer Vision (Scale-Space '03), June 2003, Isle of Skye, UK, Lecture Notes in Computer Science 2695: 683–698.
Shokoufandeh A, Macrini D, Dickinson S, Siddiqi K, Zucker SW: Indexing hierarchical structures using graph spectra. IEEE Transactions on Pattern Analysis and Machine Intelligence 2005, 27(7):1125–1140. Special issue on syntactic and structural pattern recognition
Barash D: Second eigenvalue of the Laplacian matrix for predicting RNA conformational switch by mutation. Bioinformatics 2004, 20(12):1861–1869. 10.1093/bioinformatics/bth157
Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P: Fast folding and comparison of RNA secondary structures. Monatshefte für Chemie 1994, 125(2):167–188. 10.1007/BF00818163
Le S-Y, Nussinov R, Maizel JV: Tree graphs of RNA secondary structures and their comparisons. Computers and Biomedical Research 1989, 22(5):461–473. 10.1016/0010-4809(89)90039-6
Shapiro BA: An algorithm for comparing multiple RNA secondary structures. Computer Applications in the Biosciences 1988, 4(3):387–393.
Margalit H, Shapiro BA, Oppenheim AB, Maizel JV: Detection of common motifs in RNA secondary structures. Nucleic Acids Research 1989, 17(12):4829–4845. 10.1093/nar/17.12.4829
Jiang T, Lin G, Ma B, Zhang K: A general edit distance between RNA structures. Journal of Computational Biology 2002, 9(2):371–388. 10.1089/10665270252935511
Kitagawa J, Futamura Y, Yamamoto K: Analysis of the conformational energy landscape of human snRNA with a metric based on tree representation of RNA structures. Nucleic Acids Research 2003, 31(7):2006–2013. 10.1093/nar/gkg288
Shapiro BA, Zhang K: Comparing multiple RNA secondary structures using tree comparisons. Computer Applications in the Biosciences 1990, 6(4):309–318.
Fiedler M: Algebraic connectivity of graphs. Czechoslovak Mathematical Journal 1973, 23: 298–305.
Grone R, Merris R, Sunder VS: The Laplacian spectrum of a graph. SIAM Journal on Matrix Analysis and Applications 1990, 11(2):218–238. 10.1137/0611016
Grone R, Merris R: Algebraic connectivity of trees. Czechoslovak Mathematical Journal 1987, 37(4):660–670.
Merris R: Characteristic vertices of trees. Linear and Multilinear Algebra 1987, 22: 115–131. 10.1080/03081088708817827
Smith DB, Simmonds P: Characteristics of nucleotide substitution in the hepatitis C virus genome: constraints on sequence change in coding regions at both ends of the genome. Journal of Molecular Evolution 1997, 45(3):238–246. 10.1007/PL00006226
You S, Stump DD, Branch AD, Rice CM: A cis -acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for Hepatitis C virus RNA replication. Journal of Virology 2004, 78(3):1352–1366. 10.1128/JVI.78.3.1352-1366.2004
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Churkin, A., Barash, D. Structural Analysis of Single-Point Mutations Given an RNA Sequence: A Case Study with RNAMute. EURASIP J. Adv. Signal Process. 2006, 056246 (2006) doi:10.1155/ASP/2006/56246
- Escherichia Coli
- Structural Change
- Information Technology
- Structural Analysis
- Functional Analysis