title: In NF1, CFTR, PER3, CARS and SYT7, alternatively included exons show higher conservation of surrounding intron sequences than constitutive exons.
abstract: It is still not fully understood to what extent intronic sequences contribute to the regulation of the different forms of alternative splicing. We are interested in the regulation of alternative cassette exon events, such as exon inclusion and exon skipping. We investigated these events by comparative genomic analysis of human and mouse in five experimentally well-characterized genes, neurofibromatosis 1 (NF1), cystic fibrosis transmembrane conductance regulator (CFTR), period 3 (PER3), cysteinyl-tRNA synthetase (CARS) and synaptotagmin 7 (SYT7). In NF1, high intron identity around the 52 constitutive and four alternatively skipped NF1 exons is restricted to the close vicinity of the exons. In contrast, we found on average high conservation of intron sequences over 300 base pairs up- and downstream of the five alternatively included NF1 exons. The investigation of alternatively included exons in CFTR, PER3, CARS and SYT7 supported this finding. In contrast, the mean intron identities around the alternatively skipped exons in CTFR and NF1 do not differ considerably from those around the constitutive exons. In these genes, the difference in intron conservation could point to a difference between the regulation of alternative exon inclusion and alternative exon skipping or constitutive exon splicing. Additional genome-wide investigations are necessary to elucidate to what extent our finding can be generalized.
authors.affiliation: Department of Human Genetics, University of Ulm, Germany. dieter.kaufmann@medizin.uni-ulm.de
authors.forename: Dieter
authors.initials: D
authors.lastname: Kaufmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Kenner
authors.forename: Peter
authors.initials: P
authors.lastname: Nurnberg
authors.forename: Walther
authors.initials: W
authors.lastname: Vogel
authors.forename: Britta
authors.initials: B
authors.lastname: Bartelt
mesh_terms: D017398:Alternative Splicing; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D017931:DNA Primers; D005091:Exons; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D012689:Sequence Homology, Nucleic Acid; D050857:Synaptotagmins; D014157:Transcription Factors
chemical_list: C505032:CFTR protein, human; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C512644:PER3 protein, human; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; C494302:SYT7 protein, human; C494303:Syt7 protein, mouse; D014157:Transcription Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D050857:Synaptotagmins; D000604:Amino Acyl-tRNA Synthetases; C019975:cysteinyl-tRNA synthetase