title: Unconstrained mining of transcript data reveals increased alternative splicing complexity in the human transcriptome.
abstract: Mining massive amounts of transcript data for alternative splicing information is paramount to help understand how the maturation of RNA regulates gene expression. We developed an algorithm to cluster transcript data to annotated genes to detect unannotated splice variants. A higher number of alternatively spliced genes and isoforms were found compared to other alternative splicing databases. Comparison of human and mouse data revealed a marked increase, in human, of splice variants incorporating novel exons and retained introns. Previously unannotated exons were validated by tiling array expression data and shown to correspond preferentially to novel first exons. Retained introns were validated by tiling array and deep sequencing data. The majority of retained introns were shorter than 500 nt and had weak polypyrimidine tracts. A subset of retained introns matching small RNAs and displaying a high GC content suggests a possible coordination between splicing regulation and production of noncoding RNAs. Conservation of unannotated exons and retained introns was higher in horse, dog and cow than in rodents, and 64% of exon sequences were only found in primates. This analysis highlights previously bypassed alternative splice variants, which may be crucial to deciphering more complex pathways of gene regulation in human.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. ines.mollet@med.lu.se
authors.forename: I G
authors.initials: IG
authors.lastname: Mollet
authors.forename: Claudia
authors.initials: C
authors.lastname: Ben-Dov
authors.forename: Daniel
authors.initials: D
authors.lastname: Felício-Silva
authors.forename: A R
authors.initials: AR
authors.lastname: Grosso
authors.forename: Pedro
authors.initials: P
authors.lastname: Eleutério
authors.forename: Ruben
authors.initials: R
authors.lastname: Alves
authors.forename: Ray
authors.initials: R
authors.lastname: Staller
authors.forename: Tito Santos
authors.initials: TS
authors.lastname: Silva
authors.forename: Maria
authors.initials: M
authors.lastname: Carmo-Fonseca
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D017124:Conserved Sequence; D057225:Data Mining; D005091:Exons; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods; D006801:Humans; D007438:Introns; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry; D022661:RNA, Untranslated / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D022661:RNA, Untranslated
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