The Community for Technology Leaders
RSS Icon
Subscribe
Issue No.04 - July-Aug. (2013 vol.10)
pp: 832-844
Ronny Lorenz , Dept. of Theor. Chem., Univ. of Vienna, Vienna, Austria
Stephan H. Bernhart , Dept. of Comput. Sci., Univ. of Leipzig, Leipzig, Germany
Jing Qin , Max Planck Inst. for Math. in the Sci., Leipzig, Germany
Christian Honer Zu Siederdissen , Dept. of Theor. Chem., Univ. of Vienna, Vienna, Austria
Andrea Tanzer , Dept. of Theor. Chem., Univ. of Vienna, Vienna, Austria
Fabian Amman , Dept. of Theor. Chem., Univ. of Vienna, Vienna, Austria
Ivo L. Hofacker , Dept. of Theor. Chem., Univ. of Vienna, Vienna, Austria
Peter F. Stadler , Dept. of Comput. Sci., Univ. of Leipzig, Leipzig, Germany
ABSTRACT
G-quadruplexes are abundant locally stable structural elements in nucleic acids. The combinatorial theory of RNA structures and the dynamic programming algorithms for RNA secondary structure prediction are extended here to incorporate G-quadruplexes using a simple but plausible energy model. With preliminary energy parameters, we find that the overwhelming majority of putative quadruplex-forming sequences in the human genome are likely to fold into canonical secondary structures instead. Stable G-quadruplexes are strongly enriched, however, in the 5Ê1UTR of protein coding mRNAs.
INDEX TERMS
RNA, Shape, Bioinformatics, Temperature measurement, Computational biology, Humans, DNA,HASH(0x4eb4c2c),
CITATION
Ronny Lorenz, Stephan H. Bernhart, Jing Qin, Christian Honer Zu Siederdissen, Andrea Tanzer, Fabian Amman, Ivo L. Hofacker, Peter F. Stadler, "2D Meets 4G: G-Quadruplexes in RNA Secondary Structure Prediction", IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol.10, no. 4, pp. 832-844, July-Aug. 2013, doi:10.1109/TCBB.2013.7
REFERENCES
[1] K. Paeschke, T. Simonsson, J. Postberg, D. Rhodes, and H.J. Lipps, "Telomere End-Binding Proteins Control the Formation of G-Quadruplex DNA Structures in Vivo," Nature Structural Molecular Biology, vol. 12, pp. 847-854, 2005.
[2] J.E. Johnson, J.S. Smith, M.L. Kozak, and F.B. Johnson, "In Vivo Veritas: Using Yeast to Probe the Biological Functions of G-Quadruplexes," Biochimie, vol. 90, pp. 1250-1263, 2008.
[3] H.M. Wong, L. Payet, and J.L. Huppert, "Function and Targeting of G-Quadruplexes," Current Opinion Molecular Therapeutics, vol. 11, pp. 146-155, 2009.
[4] A. Baral, P. Kumar, R. Halder, P. Mani, V.K. Yadav, A. Singh, S.K. Das, and S. Chowdhury, "Quadruplex-Single Nucleotide Polymorphisms (Quad-SNP) Influence Gene Expression Difference among Individuals," Nucleic Acids Research, vol. 40, pp. 3800-3811, 2012.
[5] D. Gomez, A. Guédin, J.L. Mergny, B. Salles, J.F. Riou, M.P. Teulade-Fichou, and P. Calsou, "A G-Quadruplex Structure within the 5'-UTR of TRF2 mRNA Represses Translation in Human Cells," Nucleic Acids Research, vol. 38, pp. 7187-7198, 2010.
[6] M.J. Morris and S. Basu, "An Unusually Stable G-Quadruplex within the 5'-UTR of the MT3 Matrix Metalloproteinase mRNA Represses Translation in Eukaryotic Cells," Biochemistry, vol. 48, pp. 5313-5319, 2009.
[7] L. Menon and M.R. Mihailescu, "Interactions of the G Quartet Forming Semaphorin 3F RNA with the RGG Box Domain of the Fragile X Protein Family," Nucleic Acids Research, vol. 35, pp. 5379-5392, 2007.
[8] M. Bensaid, M. Melko, E.G. Bechara, L. Davidovic, A. Berretta, M.V. Catania, J. Gecz, E. Lalli, and B. Bardoni, "FRAXE-Associated Mental Retardation Protein (FMR2) Is an RNA-Binding Protein with High Affinity for G-Quartet RNA Forming Structure," Nucleic Acids Research, vol. 37, pp. 1269-1279, 2009.
[9] A. Bugaut and S. Balasubramanian, "5'-UTR RNA G-Quadruplexes: Translation Regulation and Targeting," Nucleic Acids Research, vol. 40, pp. 4727-4741, 2012.
[10] A. Arora and B. Suess, "An RNA G-Quadruplex in the 3' UTR of the Proto-Oncogene PIM1 Represses Translation," RNA Biology, vol. 8, pp. 802-805, 2011.
[11] J.L. Huppert, A. Bugaut, S. Kumari, and S. Balasubramanian, "G-Quadruplexes: The Beginning and End of UTRs," Nucleic Acids Research, vol. 36, pp. 6260-6268, 2008.
[12] J.D. Beaudoin and J.P. Perreault, "5'-UTR G-Quadruplex Structures Acting as Translational Repressors," Nucleic Acids Research, vol. 38, pp. 7022-7036, 2010.
[13] M. Wieland and J.S. Hartig, "RNA Quadruplex-Based Modulation of Gene Expression," Chemistry Biology, vol. 14, pp. 757-763, 2007.
[14] G.G. Jayaraj, S. Pandey, V. Scaria, and S. Maiti, "Potential G-Quadruplexes in the Human Long Non-Coding Transcriptome," RNA Biology, vol. 9, pp. 81-86, 2012.
[15] B. Luke and J. Lingner, "TERRA: Telomeric Repeat-Containing RNA," EMBO J., vol. 28, pp. 2503-2510, 2009.
[16] A.Y. Zhang, A. Bugaut, and S. Balasubramanian, "A Sequence-Independent Analysis of the Loop Length Dependence of Intramolecular RNA G-Quadruplex Stability and Topology," Biochemistry, vol. 50, pp. 7251-7258, 2011.
[17] M. Webba da Silva, "Geometric Formalism for DNA Quadruplex Folding," Chemistry, vol. 13, pp. 9738-9745, 2007.
[18] D.H. Zhang and G.Y. Zhi, "Structure Monomorphism of RNA G-Quadruplex That Is Independent of Surrounding Condition," J. Biotechnology, vol. 150, pp. 6-10, 2010.
[19] J. Eddy and N. Maizels, "Gene Function Correlates with Potential for G4 DNA Formation in the Human Genome," Nucleic Acids Research, vol. 34, pp. 3887-3896, 2006.
[20] J.L. Huppert and S. Balasubramanian, "Prevalence of Quadruplexes in the Human Genome," Nucleic Acids Research, vol. 33, pp. 2908-2916, 2005.
[21] Y. Zhao, Z. Du, and N. Li, "Extensive Selection for the Enrichment of G4 DNA Motifs in Transcriptional Regulatory Regions of Warm Blooded Animals," FEBS Letters, vol. 581, pp. 1951-1956, 2007.
[22] A. Verma, K. Halder, R. Halder, V.K. Yadav, P. Rawal, R.K. Thakur, F. Mohd, A. Sharma, and S. Chowdhury, "G-Quadruplex DNA Motifs as Conserved Cis-Regulatory Elements," J. Medicinal Chemistry, vol. 51, pp. 5641-5649, 2008.
[23] O. Kikin, L. D'Antonio, and P.S. Bagga, "QGRS Mapper: A Web-Based Server for Predicting G-Quadruplexes in Nucleotide Sequences," Nucleic Acids Research, vol. 34, pp. W676-W682, 2006.
[24] A.K. Todd, "Bioinformatics Approaches to Quadruplex Sequence Location," Methods, vol. 43, pp. 246-251, 2007.
[25] O. Stegle, L. Payet, J.-L. Mergny, D.J.C. MacKay, and J.L. Huppert, "Predicting and Understanding the Stability of G-Quadruplexes," Bioinformatics, vol. 25, pp. i374-i382, 2009.
[26] R. Lorenz, S.H. Bernhart, F. Externbrink, J. Qin, C. Höner zu Siederdissen, F. Amman, I.L. Hofacker, and P.F. Stadler, "RNA Folding Algorithms with G-Quadruplexes," Proc. Brazilian Symp. Bioinformatics (BSB '12), M.C.P. de Souto and M.G. Kann, eds., pp. 49-60, 2012.
[27] J.L. Mergny and L. Lacroix, "UV Melting of G-Quadruplexes," Current Protocols in Nucleic Acid Chemistry, Unit 17.1, Wiley, 2009.
[28] A. Bugaut and S. Balasubramanian, "A Sequence-Independent Study of the Influence of Short Loop Lengths on the Stability and Topology of Intramolecular DNA G-Quadruplexes," Biochemistry, vol. 47, pp. 689-697, 2008.
[29] D.H. Zhang, T. Fujimoto, S. Saxena, H.Q. Yu, D. Miyoshi, and N. Sugimoto, "Monomorphic RNA G-Quadruplex and Polymorphic DNA G-Quadruplex Structures Responding to Cellular Environmental Factors," Biochemistry, vol. 49, pp. 4554-4563, 2010.
[30] A. Guédin, A. De Cian, J. Gros, L. Lacroix, and J.L. Mergny, "Sequence Effects in Single-Base Loops for Quadruplexes," Biochimie, vol. 90, pp. 686-696, 2008.
[31] A. Guédin, J. Gros, A. Patrizia, and J.-L. Mergny, "How Long Is Too Long? Effects of Loop Size on G-Quadruplex Stability," Nucleic Acids Research, vol. 38, pp. 7858-7868, 2010.
[32] C.T. Lauhon and J.W. Szostak, "RNA Aptamers that Bind Flavin and Nicotinamide Redox Cofactors," J. Am. Chemical Soc., vol. 117, pp. 1246-1257, 1995.
[33] A. Joachimi, A. Benz, and J.S. Hartig, "A Comparison of DNA and RNA Quadruplex Structures and Stabilities," Bioorganic Medicinal Chemistry, vol. 17, pp. 6811-6815, 2009.
[34] R. Lorenz, S.H. Bernhart, C. Höner zu Siederdissen, H. Tafer, C. Flamm, P.F. Stadler, and I.L. Hofacker, "ViennaRNA Package 2.0," Algorithms Molecular Biology, vol. 6, article 26, 2011.
[35] P. Schuster, W. Fontana, P.F. Stadler, and I.L. Hofacker, "From Sequences to Shapes and Back: A Case Study in RNA Secondary Structures," Proc. Royal Soc. London B, vol. 255, pp. 279-284, 1994.
[36] R. Giegerich, B. Voss, and M. Rehmsmeier, "Abstract Shapes of RNA," Nucleic Acids Research, vol. 32, pp. 4843-4851, 2004.
[37] P. Flajolet and R. Sedgewick, Analytic Combinatorics. Cambridge Univ. Press, 2009.
[38] I.L. Hofacker, P. Schuster, and P.F. Stadler, "Combinatorics of RNA Secondary Structures," Discrete Applied Math., vol. 88, pp. 207-237, 1998.
[39] D.H. Mathews, M.D. Disney, J.L. Childs, S.J. Schroeder, M. Zuker, and D.H. Turner, "Incorporating Chemical Modification Constraints into a Dynamic Programming Algorithm for Prediction of RNA Secondary Structure," Proc. Nat'l Academy Sciences USA, vol. 101, pp. 7287-7292, 2004.
[40] M. Zuker and P. Stiegler, "Optimal Computer Folding of Large RNA Sequences Using Thermodynamics and Auxiliary Information," Nucleic Acids Research, vol. 9, pp. 133-148, 1981.
[41] J.S. McCaskill, "The Equilibrium Partition Function and Base Pair Binding Probabilities for RNA Secondary Structure," Biopolymers, vol. 29, pp. 1105-1119, 1990.
[42] R.E. Bruccoleri and G. Heinrich, "An Improved Algorithm for Nucleic Acid Secondary Structure Display," Computer Application Biosciences, vol. 4, pp. 167-173, 1988.
[43] C.B. Do, D.A. Woods, and S. Batzoglou, "CONTRAfold: RNA Secondary Structure Prediction without Physics-Based Models," Bioinformatics, vol. 22, no. 14, pp. e90-e98, 2006.
[44] S. Kumari, A. Bugaut, J.L. Huppert, and S. Balasubramanian, "An RNA G-Quadruplex in the 5'UTR of the NRAS Proto-Oncogene Modulates Translation," Nat'l Chemical Biology, vol. 3, pp. 218-221, 2007.
[45] I.L. Hofacker, B. Priwitzer, and P.F. Stadler, "Prediction of Locally Stable RNA Secondary Structures for Genome-Wide Surveys," Bioinformatics, vol. 20, pp. 191-198, 2004.
[46] S. Bernhart, I.L. Hofacker, and P.F. Stadler, "Local RNA Base Pairing Probabilities in Large Sequences," Bioinformatics, vol. 22, pp. 614-615, 2006.
[47] S.H. Bernhart, H. Tafer, U. Mückstein, C. Flamm, P.F. Stadler, and I.L. Hofacker, "Partition Function and Base Pairing Probabilities of RNA Heterodimers," Algorithms Molecular Biology, vol. 1, article 3, 2006.
[48] U. Mückstein, H. Tafer, J. Hackermüller, S.B. Bernhard, P.F. Stadler, and I.L. Hofacker, "Thermodynamics of RNA-RNA Binding," Bioinformatics, vol. 22, pp. 1177-1182, 2006.
[49] A. Busch, A. Richter, and R. Backofen, "IntaRNA: Efficient Prediction of Bacterial sRNA Targets Incorporating Target Site Accessibility and Seed Regions," Bioinformatics, vol. 24, pp. 2849-2856, 2008.
[50] M. Rehmsmeier, P. Steffen, M. Höchsmann, and R. Giegerich, "Fast and Effective Prediction of MicroRNA/Target Duplexes," RNA, vol. 10, pp. 1507-1517, 2004.
[51] K. Ito, S. Go, M. Komiyama, and Y. Xu, "Inhibition of Translation by Small RNA-Stabilized mRNA Structures in Human Cells," J. Am. Chemical Soc., vol. 133, pp. 19153-19159, 2011.
[52] H. Tafer, F. Ammann, F. Eggenhoffer, P.F. Stadler, and I.L. Hofacker, "Fast Accessibility-Based Prediction of RNA-RNA Interactions," Bioinformatics, vol. 27, pp. 1934-1940, 2011.
[53] D. Pervouchine, "IRIS: Intermolecular RNA Interaction Search," Proc. Int'l Conf. Genome Informatics, vol. 15, pp. 92-101, 2004.
[54] C. Alkan, E. Karakoc, J. Nadeau, S. Sahinalp, and K. Zhang, "RNA-RNA Interaction Prediction and Antisense RNA Target Search," J. Computational Biology, vol. 13, pp. 267-282, 2006.
[55] H. Chitsaz, R. Salari, S. Sahinalp, and R. Backofen, "A Partition Function Algorithm for Interacting Nucleic Acid Strands," Bioinformatics, vol. 25, pp. i365-i373, 2009.
[56] F.W.D. Huang, J. Qin, C.M. Reidys, and P.F. Stadler, "Partition Function and Base Pairing Probabilities for RNA-RNA Interaction Prediction," Bioinformatics, vol. 25, pp. 2646-2654, 2009.
[57] F.W.D. Huang, J. Qin, C.M. Reidys, and P.F. Stadler, "Target Prediction and a Statistical Sampling Algorithm for RNA-RNA Interaction," Bioinformatics, vol. 26, pp. 175-181, 2010.
[58] I.L. Hofacker, M. Fekete, and P.F. Stadler, "Secondary Structure Prediction for Aligned RNA Sequences," J. Molecular Biology, vol. 319, pp. 1059-1066, 2002.
[59] S.H. Bernhart, I.L. Hofacker, S. Will, A.R. Gruber, and P.F. Stadler, "RNAalifold: Improved Consensus Structure Prediction for RNA Alignments," BMC Bioinformatics, vol. 9, article 474, 2008.
[60] S.W. Burge, J. Daub, R. Eberhardt, J. Tate, L. Barquist, E.P. Nawrocki, S.R. Eddy, P.P. Gardner, and A. Bateman, "Rfam 11.0: 10 Years of RNA Families," Nucleic Acids Research, vol. 41, pp. D226-D232, 2012.
[61] T.W. Harris, I. Antoshechkin, T. Bieri, D. Blasiar, J. Chan, W.J. Chen, N. De La Cruz, P. Davis, M. Duesbury, R. Fang, J. Fernandes, M. Han, R. Kishore, R. Lee, H.M. Müller, C. Nakamura, P. Ozersky, A. Petcherski, A. Rangarajan, A. Rogers, G. Schindelman, E.M. Schwarz, M.A. Tuli, K. Van Auken, D. Wang, X. Wang, G. Williams, K. Yook, R. Durbin, L.D. Stein, J. Spieth, and P.W. Sternberg, "WormBase: A Comprehensive Resource for Nematode Research," Nucleic Acids Research, vol. 38, pp. D463-D467, 2010.
[62] P. McQuilton, S.E.S. Pierre, J. Thurmond, and the FlyBase Consortium, "FlyBase 101—The Basics of Navigating FlyBase," Nucleic Acids Research, vol. 40, pp. D706-D714, 2012.
[63] P. Flicek, M. Amode, D. Barrell, K. Beal, S. Brent, D. Carvalho-Silva, P. Clapham, G. Coates, S. Fairley, S. Fitzgerald, L. Gil, L. Gordon, M. Hendrix, T. Hourlier, N. Johnson, A.K. Kähäri, D. Keefe, S. Keenan, R. Kinsella, M. Komorowska, G. Koscielny, E. Kulesha, P. Larsson, I. Longden, W. McLaren, M. Muffato, B. Overduin, M. Pignatelli, B. Pritchard, H.S. Riat, G.R. Ritchie, M. Ruffier, M. Schuster, D. Sobral, Y.A. Tang, K. Taylor, S. Trevanion, J. Vandrovcova, S. White, M. Wilson, S.P. Wilder, B.L. Aken, E. Birney, F. Cunningham, I. Dunham, R. Durbin, X.M. Fernández-Suarez, J. Harrow, J. Herrero, T.J. Hubbard, A. Parker, G. Proctor, G. Spudich, J. Vogel, A. Yates, A. Zadissa, and S.M. Searle, "Ensembl 2012," Nucleic Acids Research, vol. 40, pp. D84-D90, 2012.
[64] A.R. Quinlan and I.M. Hall, "Bedtools: A Flexible Suite of Utilities for Comparing Genomic Features," Bioinformatics, vol. 26, pp. 841-842, 2010.
[65] J. Gros, A. Guédin, J.-L. Mergny, and L. Lacroix, "G-Quadruplex Formation Interferes with P1 Helix Formation in the RNA Component of Telomerase hTERC," ChemBioChem, vol. 9, pp. 2075-2079, 2008.
[66] S.C.J. Parker, E.H. Margulies, and T.D. Tullius, "The Relationship between Fine Scale DNA Structure, GC Content, and Functional Elements in $1\%$ of the Human Genome," Genome Informatics, vol. 20, pp. 199-211, 2008.
[67] A. Arora, M. Dutkiewicz, V. Scaria, M. Hariharan, S. Maiti, and J. Kurreck, "Inhibition of Translation in Living Eukaryotic Cells by an RNA G-Quadruplex Motif," RNA, vol. 14, pp. 1290-1296, 2008.
[68] R. Shahid, A. Bugaut, and S. Balasubramanian, "The BCL-2 5' Untranslated Region Contains an RNA G-Quadruplex-Forming Motif That Modulates Protein Expression," Biochemistry, vol. 49, pp. 8300-8306, 2010.
[69] K. Halder, M. Wieland, and J.S. Hartig, "Predictable Suppression of Gene Expression by 5'-UTR-Based RNA Quadruplexes," Nucleic Acids Research, vol. 37, no. 20, pp. 6811-6817, 2009.
[70] S. Lammich, F. Kamp, J. Wagner, B. Nuscher, S. Zilow, A.-K. Ludwig, M. Willem, and C. Haass, "Translational Repression of the Disintegrin and Metalloprotease ADAM10 by a Stable G-Quadruplex Secondary Structure in Its 5'-Untranslated Region," J. Biological Chemistry, vol. 286, pp. 45063-45072, 2011.
[71] M.J. Morris, Y. Negishi, C. Pazsint, J.D. Schonhoft, and S. Basu, "An RNA G-Quadruplex Is Essential for Cap-Independent Translation Initiation in Human VEGF IRES," J. Am. Chemical Soc., vol. 132, pp. 17831-17839, 2010.
[72] P.R. Wills, "Potential Pseudoknots in the PrP-Encoding mRNA," J. Theoretical Biology, vol. 159, pp. 523-527, 1992.
[73] I. Barrette, G. Poisson, P. Gendron, and F. Major, "Pseudoknots in Prion Protein mRNAs Confirmed by Comparative Sequence Analysis and Pattern Searching," Nucleic Acids Research, vol. 29, pp. 753-758, 2001.
[74] P. Cavaliere, B. Pagano, V. Granata, S. Prigent, H. Rezaei, C. Giancola, and A. Zagari, "Cross-Talk between Prion Protein and Quadruplex-Forming Nucleic Acids: A Dynamic Complex Formation," Nucleic Acids Research, vol. 41, pp. 327-339, 2013.
[75] J.A. Capra, K. Paeschke, M. Singh, and V.A. Zakian, "G-Quadruplex DNA Sequences Are Evolutionarily Conserved and Associated with Distinct Genomic Features in Saccharomyces cerevisiae," PLoS Computational Biology, vol. 6, article e1000861, 2010.
108 ms
(Ver 2.0)

Marketing Automation Platform Marketing Automation Tool