title: Trans-acting factors may cause dystrophin splicing misregulation in BMD skeletal muscles.
abstract: We analyzed dystrophin alternative splicing events in a large number of Becker muscular dystrophy (BMD) affected individuals presenting major hot-spot deletions. Evidence is shown that altered splicing patterns in these patients do not directly result from the gene defect but probably derive from modifications in trans- rather than cis-acting factors. Several potential CUG-binding protein 2 (CUG-BP2) binding sites were found to be located in the dystrophin gene region encompassing exons 43-60 and CUG-BP2 transcript analysis indicated that not only expression levels are increased in dystrophic muscles but also that different CUG-BP2 isoforms are expressed. The possibility that CUG-BP2 might have a role in dystrophin splicing regulation is discussed.
authors.affiliation: IRCCS E. Medea, Associazione La Nostra Famiglia, Via Don Luigi Monza 20, 23842 Bosisio Parini (LC), Italy. msironi@bp.lnf.it
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: R
authors.initials: R
authors.lastname: Cagliani
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
authors.forename: U
authors.initials: U
authors.lastname: Pozzoli
authors.forename: A
authors.initials: A
authors.lastname: Bardoni
authors.forename: R
authors.initials: R
authors.lastname: Giorda
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D016189:Dystrophin; D012333:RNA, Messenger