title: Computational identification of tissue-specific alternative splicing elements in mouse genes from RNA-Seq.
abstract: Tissue-specific alternative splicing is a key mechanism for generating tissue-specific proteomic diversity in eukaryotes. Splicing regulatory elements (SREs) in pre-mature messenger RNA play a very important role in regulating alternative splicing. In this article, we use mouse RNA-Seq data to determine a positive data set where SREs are over-represented and a reliable negative data set where the same SREs are most likely under-represented for a specific tissue and then employ a powerful discriminative approach to identify SREs. We identified 456 putative splicing enhancers or silencers, of which 221 were predicted to be tissue-specific. Most of our tissue-specific SREs are likely different from constitutive SREs, since only 18% of our exonic splicing enhancers (ESEs) are contained in constitutive RESCUE-ESEs. A relatively small portion (20%) of our SREs is included in tissue-specific SREs in human identified in two recent studies. In the analysis of position distribution of SREs, we found that a dozen of SREs were biased to a specific region. We also identified two very interesting SREs that can function as an enhancer in one tissue but a silencer in another tissue from the same intronic region. These findings provide insight into the mechanism of tissue-specific alternative splicing and give a set of valuable putative SREs for further experimental investigations.
authors.affiliation: Department of Electrical and Computer Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, FL 33146, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Wen
authors.forename: Akira
authors.initials: A
authors.lastname: Chiba
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cai
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism; D019295:Computational Biology; D005091:Exons; D008099:Liver / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D012322:RNA Precursors / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry; D038621:Regulatory Sequences, Ribonucleic Acid; D017423:Sequence Analysis, RNA
chemical_list: D011506:Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid