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A Method to Predict the Structure and Stability of RNA/RNA Complexes

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RNA Structure Determination

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1490))

Abstract

RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop–loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop–loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities. The method is based on the virtual bond RNA folding model (Vfold). The main emphasis in the method is placed on the evaluation of the entropy and free energy for the loops, especially tertiary kissing loops. The method also uses recursive partition function calculations and two-step screening algorithm for large, complicated structures of RNA/RNA complexes. As case studies, we use the HIV-1 Mal dimer and the siRNA/HIV-1 mutant (T4) to illustrate the method.

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References

  1. Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336

    Article  CAS  PubMed  Google Scholar 

  2. Roy SW, Gilbert W (2006) The evolution of spliceosomal introns: patterns, puzzles and progress. Nat Rev Genet 7:211–221

    PubMed  Google Scholar 

  3. Taggart AJ, DeSimone AM, Shih JS, Filloux ME, Fairbrother WG (2012) Large-scale mapping of branchpoints in human pre-mRNA transcripts in vivo. Nat Struct Mol Biol 19:719–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39:1278–1284

    Article  CAS  PubMed  Google Scholar 

  5. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379

    Article  CAS  PubMed  Google Scholar 

  7. Westerhout EM, Berkhout B (2007) A systematic analysis of the effect of target RNA structure on RNA interference. Nucleic Acids Res 35:4322–4330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Russell RS, Liang C, Wainberg MA (2004) Is HIV-1 RNA dimerization a prerequisite for packaging? Yes, no, probably? Retrovirology 1:23

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lorenz C, Piganeau N, Schroeder R (2006) Stabilities of HIV-1 DIS type RNA loop-loop interactions in vitro and in vivo. Nucleic Acids Res 34:334–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Paillart JC, Shehu-Xhilaga M, Marquet R, Mak J (2004) Dimerization of retroviral RNA genomes: an inseparable pair. Nat Rev Microbiol 2:461–472

    Article  CAS  PubMed  Google Scholar 

  11. Cao S, Chen S-J (2006) Free energy landscapes of RNA/RNA complexes: with applications to snRNA complexes in spliceosomes. J Mol Biol 357:292–312

    Article  CAS  PubMed  Google Scholar 

  12. Cao S, Chen S-J (2012) Predicting kissing interactions in microRNA-target complex and assessment of microRNA activity. Nucleic Acids Res 40: 4681–4690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cao S, Chen S-J (2011) Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal. RNA 17:2130–2143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cao S, Xu X, Chen S-J (2014) Predicting structure and stability for RNA complexes with intermolecular loop-loop base-pairing. RNA 20 835–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Andronescu MS, Zhang ZC, Condon AE (2005) Secondary structure prediction of interacting RNA molecules. J Mol Biol 345:987–1001

    Article  CAS  PubMed  Google Scholar 

  16. Bernhart SH, Tafer H, Flamm C, Stadler PF, Hofacker IL (2006) Partition function and base pairing probabilities of RNA heterodimers. Algorithms Mol Biol 1:3

    Article  PubMed  PubMed Central  Google Scholar 

  17. Dirks RM, Bois JS, Schaeffer JM, Winfree E, Pierce NA (2007) Thermodynamic analysis of interacting nucleic acid strands. SIAM Rev 49:65–88

    Article  Google Scholar 

  18. Dimitrov RA, Zuker M (2004) Prediction of hybridization and melting for double-stranded nucleic acids. Biophys J 87:215–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mathews DH (2010) Using OligoWalk to identify efficient siRNA sequences. Methods Mol Biol 629:109–121

    PubMed  Google Scholar 

  20. Andronescu MS, Pop C, Condon AE (2010) Improved free energy parameters for RNA pseudoknotted secondary structure prediction. RNA 16:26–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Huang FWD, Qin J, Reidys CM, Stadler PF (2009) Partition function and base pairing probabilities for RNA–RNA interaction prediction. Bioinformatics 25:2646–2654

    Article  CAS  PubMed  Google Scholar 

  22. Chitsaz H, Salari R, Sahinalp SC, Backofen R (2009) A partition function algorithm for interacting nucleic acid strands. Bioinformatics 25(12):i365–i373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cao S, Chen S-J (2005) Predicting RNA folding thermodynamics with a reduced chain representation model. RNA 11:1884–1897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen S-J (2008) RNA folding: conformational statistics, folding kinetics, and ion electrostatics. Annu Rev Biophys 37:197–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xu X, Zhao P, Chen S-J (2014) Vfold: a web server for RNA structure and folding thermodynamics prediction. PLoS One 9:e107504

    Article  PubMed  PubMed Central  Google Scholar 

  26. Xu X, Chen S-J (2012) Kinetic mechanism of conformational switch between bistable RNA hairpins. J Am Chem Soc 134:12499–12507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cao S, Chen S-J (2006) Predicting RNA pseudoknot folding thermodynamics. Nucleic Acids Res 34:2634–2652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cao S, Chen S-J (2009) Predicting structures and stabilities for H-type pseudoknots with inter-helix loop. RNA 15:696–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cao S, Chen S-J (2012) A domain-based model for predicting large and complex pseudoknotted structures. RNA Biol 9:200–211

    Article  PubMed  Google Scholar 

  30. Turner DH, Mathews DH (2010) NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res 38:D280–D282

    Article  CAS  PubMed  Google Scholar 

  31. Ennifar E, Walter P, Ehresmann B, Ehresmann C, Dumas P (2001) Crystal structures of coaxially stacked kissing complexes of the HIV-1 RNA dimerization initiation site. Nat Struct Biol 8:1064–1068

    Article  CAS  PubMed  Google Scholar 

  32. Muriaux D, De Rocquigny H, Roques BP, Paoletti J (1996) NCp7 activates HIV-1Lai RNA dimerization by converting a transient loop-loop complex into a stable dimer. J Biol Chem 271:33686–33692

    Article  CAS  PubMed  Google Scholar 

  33. Arnott S, Hukins DW, Dover SD (1972) Optimised parameters for RNA double-helices. Biochem Biophys Res Commun 48:1392–1399

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Physics, Informatics Institute, University of Missouri, Columbia, MI, USA

    Xiaojun Xu & Shi-Jie Chen

  2. Department of Biochemistry, Informatics Institute, University of Missouri, Columbia, MI, USA

    Xiaojun Xu & Shi-Jie Chen

  3. Center for RNA Biology, University of Rochester Medical Center, Rochester, NY, USA

    Xiaojun Xu & Shi-Jie Chen

Authors
  1. Xiaojun Xu
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  2. Shi-Jie Chen
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Editor information

Editors and Affiliations

  1. Department of Chemistry and Center for RNA Biology, University of Rochester College of Arts and Sciences, Rochester, New York, USA

    Douglas H. Turner

  2. Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, New York, USA

    David H. Mathews

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Xu, X., Chen, SJ. (2016). A Method to Predict the Structure and Stability of RNA/RNA Complexes. In: Turner, D., Mathews, D. (eds) RNA Structure Determination. Methods in Molecular Biology, vol 1490. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6433-8_5

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  • DOI: https://doi.org/10.1007/978-1-4939-6433-8_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6431-4

  • Online ISBN: 978-1-4939-6433-8

  • eBook Packages: Springer Protocols

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