Analysing RNA-kinetics based on folding space abstraction

BMC Bioinformatics

Jiabin Huang¹  Björn Voß¹ 

[1] Genetics & Experimental Bioinformatics, Faculty of Biology, University of Freiburg, Schänzlestr. 1, 79104, Freiburg, Germany

关键词: Abstraction;    Kinetics;    Folding space;    RNA;   

Others  :  1087608
DOI  :  10.1186/1471-2105-15-60

 received in 2013-09-09, accepted in 2014-02-24,  发布年份 2014

【 摘 要 】

Background

RNA molecules, especially non-coding RNAs, play vital roles in the cell and their biological functions are mostly determined by structural properties. Often, these properties are related to dynamic changes in the structure, as in the case of riboswitches, and thus the analysis of RNA folding kinetics is crucial for their study. Exact approaches to kinetic folding are computationally expensive and, thus, limited to short sequences. In a previous study, we introduced a position-specific abstraction based on helices which we termed helix index shapes (hishapes) and a hishape-based algorithm for near-optimal folding pathway computation, called HiPath. The combination of these approaches provides an abstract view of the folding space that offers information about the global features.

Results

In this paper we present HiKinetics, an algorithm that can predict RNA folding kinetics for sequences up to several hundred nucleotides long. This algorithm is based on RNAHeliCes, which decomposes the folding space into abstract classes, namely hishapes, and an improved version of HiPath, namely HiPath2, which estimates plausible folding pathways that connect these classes. Furthermore, we analyse the relationship of hishapes to locally optimal structures, the results of which strengthen the use of the hishape abstraction for studying folding kinetics. Finally, we show the application of HiKinetics to the folding kinetics of two well-studied RNAs.

Conclusions

HiKinetics can calculate kinetic folding based on a novel hishape decomposition. HiKinetics, together with HiPath2 and RNAHeliCes, is available for download at http://www.cyanolab.de/software/RNAHeliCes.htm webcite.

【 授权许可】

   
2014 Huang and Voß; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Flamm C, Fontana W, Hofacker IL, Schuster P: RNA folding at elementary step resolution. RNA 2000, 6(3):325-338.
• [2]Schmitz M, Steger G: Description of RNA folding by “simulated annealing”. J Mol Biol 1996, 255(1):254-266.
• [3]Danilova LV, Pervouchine DD, Favorov AV, Mironov AA: RNAKinetics: a web server that models secondary structure kinetics of an elongating RNA. J Bioinformatics and Comput Biol 2006, 4(02):589-596.
• [4]Wolfinger MT, Svrcek-Seiler WA, Flamm C, Hofacker IL, Stadler PF: Efficient computation of RNA folding dynamics. J Phys A: Math and General 2004, 37(17):4731.
• [5]Cao S, Chen SJ: Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. J Mol Biol 2007, 367(3):909-924.
• [6]Tang XY, Thomas S, Tapia L, Giedroc DP, Amato NM: Simulating RNA folding kinetics on approximated energy landscapes. J Mol Biol 2008, 381(4):1055-1067.
• [7]Tang XY, Kirkpatrick B, Thomas S, Song G, Amato NM: Using motion planning to study RNA folding kinetics. J Comput Biol 2005, 12(6):862-881.
• [8]Flamm C, Hofacker IL, Stadler PF, Wolfinger MT: Barrier trees of degenerate landscapes. Z Phys Chem 2002, 216(2/2002):155.
• [9]Maňuch J, Thachuk C, Stacho L, Condon A: NP-completeness of the energy barrier problem without pseudoknots and temporary arcs. Natural Comput 2011, 10(1):391-405.
• [10]Morgan SR, Higgs PG: Barrier heights between ground states in a model of RNA secondary structure. J Phys A-Math Gen 1998, 31:3153.
• [11]Flamm C, Hofacker IL, Maurer-Stroh S, Stadler PF, Zehl M: Design of multistable RNA molecules. RNA 2001, 7(2):254-265.
• [12]Dotu I, Lorenz WA, Hentenryck PV, Clote P: Computing folding pathways between RNA secondary structures. Nucleic Acids Res 2010, 38(5):1711-1722.
• [13]Li Y, Zhang SJ: Predicting folding pathways between RNA conformational structures guided by RNA stacks. BMC Bioinformatics 2012, 13(Suppl 3):5. BioMed Central Full Text
• [14]Huang J, Backofen R, Voß B: Abstract folding space analysis based on helices. RNA 2012, 18(12):2135-2147.
• [15]Nebel ME, Scheid A: On quantitative effects of RNA shape abstraction. Theor Biosci 2009, 128(4):211-225.
• [16]Lorenz WA, Clote P: Computing the partition function for kinetically trapped RNA secondary structures. PLoS ONE 2011, 6(1):16178.
• [17]Wakeman CA, Winkler WCIII: CED: Structural features of metabolite-sensing riboswitches. Trends in Biochemical Sciences 2007, 32(9):415.
• [18]Mandal M, Boese B, Barrick JE, Winkler WC, Breaker RR: Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 2003, 113(5):577-586.
• [19]Voß B, Meyer C, Giegerich R: Evaluating the predictability of conformational switching in RNA. Bioinformatics 2004, 20(10):1573-1582.
• [20]Xia TB, SantaLucia J, Burkard ME, Kierzek R, Schroeder SJ, Jiao XQ, Cox C, Turner DH: Thermodynamic parameters for an expanded Nearest-Neighbor model for formation of RNA duplexes with Watson-Crick base pairs. Biochemistry-US 1998, 37(42):14719-14735.
• [21]Mathews DH, Sabina J, Zuker M, Turner DH: Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 1999, 288(5):911-940.
• [22]Janssen S, Schudoma C, Steger G, Giegerich R: Lost in folding space? comparing four variants of the thermodynamic model for RNA secondary structure prediction. BMC Bioinformatics 2011, 12(1):429. BioMed Central Full Text
• [23]Hofacker IL: Vienna RNA secondary structure server. Nucleic Acids Res 2003, 31(13):3429-3431.
• [24]LeCuyer KA, Crothers DM: The Leptomonas collosoma spliced leader RNA can switch between two alternate structural forms. Biochemistry-US 1993, 32(20):5301-5311.
• [25]Weinberg Z, Barrick JE, Yao Z, Roth A, Kim JN, Gore J, Wang JX, Lee ER, Block KF, Sudarsan N, Neph S, Tompa M, Ruzzo WL, Breaker RR: Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res 2007, 35(14):4809-4819.
• [26]Li Y, Zhang S: Finding stable local optimal RNA secondary structures. Bioinformatics 2011, 27(21):2994-3001.
• [27]Wickiser JK, Winkler WC, Breaker RR, Crothers DM: The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Molecular Cell 2005, 18(1):49-60.
• [28]Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, Bateman A: Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res 2005, 33(suppl 1):121-124.
• [29]Bengert P, Dandekar T: Riboswitch finder–a tool for identification of riboswitch RNAs. Nucleic Acids Res 2004, 32(suppl 2):154-159.
• [30]Abreu-Goodger C, Merino E: Ribex: a web server for locating riboswitches and other conserved bacterial regulatory elements. Nucleic Acids Res 2005, 33(suppl 2):690-692.
• [31]Chang TH, Huang HD, Wu LC, Yeh CT, Liu BJ, Horng JT: Computational identification of riboswitches based on RNA conserved functional sequences and conformations. RNA 2009, 15(7):1426-1430.
• [32]Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH: Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci USA 2004, 101(19):7287-7292.
• [33]Sauthoff G, Janssen S, Giegerich R: Bellman’s gap: a declarative language for dynamic programming. In Proceedings of the 13th International ACM SIGPLAN Symposium on Principles and Practices of Declarative Programming. New York, NY, USA: ACM; 2011:29-40.
• [34]Giegerich R, Sauthoff G: Yield grammar analysis in the Bellman’s GAP compiler. In Proceedings of the Eleventh Workshop on Language Descriptions, Tools and Applications. New York, NY, USA: ACM; 2011:7-7.
• [35]Sauthoff G, Möhl M, Janssen S, Giegerich R: Bellman’s GAP—a language and compiler for dynamic programming in sequence analysis. Bioinformatics 2013, 29(5):551-560.
• [36]Lorenz WA, Ponty Y, Clote P: Asymptotics of RNA shapes. J Comput Biol 2008, 15(1):31-63.
• [37]Dijkstra EW: A note on two problems in connexion with graphs. Numer Math 1959, 1(1):269-271.
• [38]McCaskill JS: The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 1990, 29(6-7):1105-1119.
• [39]Hyeon CB, Thirumalai D: Chain length determines the folding rates of RNA. Biophysical J 2012, 102(3):11-13.