title: IRBIS: a systematic search for conserved complementarity.
abstract: IRBIS is a computational pipeline for detecting conserved complementary regions in unaligned orthologous sequences. Unlike other methods, it follows the "first-fold-then-align" principle in which all possible combinations of complementary k-mers are searched for simultaneous conservation. The novel trimming procedure reduces the size of the search space and improves the performance to the point where large-scale analyses of intra- and intermolecular RNA-RNA interactions become possible. In this article, I provide a rigorous description of the method, benchmarking on simulated and real data, and a set of stringent predictions of intramolecular RNA structure in placental mammals, drosophilids, and nematodes. I discuss two particular cases of long-range RNA structures that are likely to have a causal effect on single- and multiple-exon skipping, one in the mammalian gene Dystonin and the other in the insect gene Ca-α1D. In Dystonin, one of the two complementary boxes contains a binding site of Rbfox protein similar to one recently described in Enah gene. I also report that snoRNAs and long noncoding RNAs (lncRNAs) have a high capacity of base-pairing to introns of protein-coding genes, suggesting possible involvement of these transcripts in splicing regulation. I also find that conserved sequences that occur equally likely on both strands of DNA (e.g., transcription factor binding sites) contribute strongly to the false-discovery rate and, therefore, would confound every such analysis. IRBIS is an open-source software that is available at http://genome.crg.es/~dmitri/irbis/.
authors.affiliation: Centre for Genomic Regulation and UPF, Barcelona 08003, Spain Faculty of Bioengineering and Bioinformatics, Moscow State University, 119992 Moscow, Russia dp@crg.eu.
authors.forename: Dmitri D
authors.initials: DD
authors.lastname: Pervouchine
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D012326:RNA Splicing / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012984:Software
chemical_list: D020537:RNA, Small Nucleolar
keywords: Ca-α1D; Dystonin; RNA–RNA interaction; alternative splicing; evolutionary conservation; exon skipping; lncRNA; long-range RNA structure; snoRNA