Abstract
RNA secondary structure plays critical roles in several biological processes. For example, many trans-acting noncoding RNA genes and cis-acting RNA regulatory elements present functional motifs, conserved both in structure and sequence, that can be hardly detected by primary sequence analysis alone. We describe here how conserved secondary structure motifs shared by functionally related RNA sequences can be detected through the software tool RNAProfile. RNAProfile takes as input a set of unaligned RNA sequences expected to share a common motif, and outputs the regions that are most conserved throughout the sequences, according to a similarity measure that takes into account both the sequence of the regions and the secondary structure they can form according to base-pairing and thermodynamic rules.
The method is split into two parts. First, it identifies candidate regions within the input sequences, and associates with each region a locally optimal secondary structure. Then, it compares candidate regions to one another, both at sequence and structure level, and builds motifs exploring the search space through a greedy heuristic. We provide a detailed guide to the different parameters that can be employed, and usage examples showing the different software capabilities.
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References
Sabin LR, Delás MJ, Hannon GJ (2013) Dogma derailed: the many influences of RNA on the genome. Mol Cell 49(5):783–794
Dieterich C, Stadler PF (2012) Computational biology of RNA interactions. Wiley Interdiscip Rev RNA 4(1):107–120
Pavesi G, Mauri G, Stefani M et al (2004) RNAProfile: an algorithm for finding conserved secondary structure motifs in unaligned RNA sequences. Nucleic Acids Res 32(10):3258–3269
Rabani M, Kertesz M, Segal E (2008) Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes. Proc Natl Acad Sci U S A 105(39):14885–14890
Hiller M, Pudimat R, Busch A et al (2006) Using RNA secondary structures to guide sequence motif finding towards single-stranded regions. Nucleic Acids Res 34(17):e117
Bafna V, Tang H, Zhang S (2006) Consensus folding of unaligned RNA sequences revisited. J Comput Biol 13(2):283–295
Mokrejs M, Vopálenský V, Kolenaty O et al (2006) IRESite: the database of experimentally verified IRES structures (www.iresite.org). Nucleic Acids Res 34(Database issue):D125–D130
Burge SW, Daub J, Eberhardt R et al (2013) Rfam 11.0: 10 years of RNA families. Nucleic Acids Res 41(Database issue):D226–D232
Grillo G, Turi A, Licciulli F et al (2010) UTRdb and UTRsite (RELEASE 2010): a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs. Nucleic Acids Res 38(Database issue):D75–D80
Reuter JS, Mathews DH (2010) RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics 11:129
Lorenz R, Bernhart SH, Höner Zu Siederdissen C et al (2011) ViennaRNA Package 2.0. Algorithms Mol Biol 6:26
Witwer C, Hofacker IL, Stadler PF (2004) Prediction of consensus RNA secondary structures including pseudoknots. IEEE/ACM Trans Comput Biol Bioinformatics 1(2):66–77
Mignone F, Gissi C, Liuni S et al (2002) Untranslated regions of mRNAs. Genome Biol 3(3):REVIEWS0004
Waterman MS (1995) Introduction to computational biology. Chapman & Hall, London
Hentze MW, Muckenthaler MU, Galy B et al (2010) Two to tango: regulation of mammalian iron metabolism. Cell 142(1):24–38
Tandara L, Salamunic I (2012) Iron metabolism: current facts and future directions. Biochem Med 22(3):311–328
Ma J, Haldar S, Khan MA et al (2012) Fe2+ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation. Proc Natl Acad Sci U S A 109(22):8417–8422
Cahill CM, Lahiri DK, Huang X et al (2009) Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Biochim Biophys Acta 1790(7):615–628
Huang TS, Melefors O, Lind MI et al (1999) An atypical iron-responsive element (IRE) within crayfish ferritin mRNA and an iron regulatory protein 1 (IRP1)-like protein from crayfish hepatopancreas. Insect Biochem Mol Biol 29(1):1–9
Lehmann R, Nüsslein-Volhard C (1991) The maternal gene nanos has a central role in posterior pattern formation of the Drosophila embryo. Development 112(3):679–691
Crucs S, Chatterjee S, Gavis ER (2000) Overlapping but distinct RNA elements control repression and activation of nanos translation. Mol Cell 5(3):457–467
Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31(13):3406–3415
Byun Y, Han K (2009) PseudoViewer3: generating planar drawings of large-scale RNA structures with pseudoknots. Bioinformatics 25(11):1435–1437
Wiese KC, Glen E, Vasudevan A (2005) JViz.Rna—a Java tool for RNA secondary structure visualization. IEEE Trans Nanobioscience 4(3):212–218
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Zambelli, F., Pavesi, G. (2015). De Novo Secondary Structure Motif Discovery Using RNAProfile. In: Picardi, E. (eds) RNA Bioinformatics. Methods in Molecular Biology, vol 1269. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2291-8_4
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DOI: https://doi.org/10.1007/978-1-4939-2291-8_4
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