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RNAmotifs: prediction of multivalent RNA motifs that control alternative splicing

Matteo Cereda123*, Uberto Pozzoli1, Gregor Rot24, Peter Juvan256, Anthony Schweitzer7, Tyson Clark7 and Jernej Ule28*

Author Affiliations

1 Scientific Institute IRCCS E. Medea, Via don L. Monza 20, 23842 Bosisio Parini, (LC), Italy

2 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK

3 Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy

4 Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

5 Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1104 Ljubljana, Slovenia

6 Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, SI-6000 Koper, Slovenia

7 Affymetrix, 3420 Central Expressway, Santa Clara, CA 95051, USA

8 Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK

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Genome Biology 2014, 15:R20  doi:10.1186/gb-2014-15-1-r20

Published: 31 January 2014

Abstract

RNA-binding proteins (RBPs) regulate splicing according to position-dependent principles, which can be exploited for analysis of regulatory motifs. Here we present RNAmotifs, a method that evaluates the sequence around differentially regulated alternative exons to identify clusters of short and degenerate sequences, referred to as multivalent RNA motifs. We show that diverse RBPs share basic positional principles, but differ in their propensity to enhance or repress exon inclusion. We assess exons differentially spliced between brain and heart, identifying known and new regulatory motifs, and predict the expression pattern of RBPs that bind these motifs. RNAmotifs is available at https://bitbucket.org/rogrro/rna_motifs webcite.