Trans-acting factors may cause dystrophin splicing misregulation in BMD skeletal muscles.
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.
Sironi
M
M
IRCCS E. Medea, Associazione La Nostra Famiglia, Via Don Luigi Monza 20, 23842 Bosisio Parini (LC), Italy. msironi@bp.lnf.it
Cagliani
R
R
Comi
G P
GP
Pozzoli
U
U
Bardoni
A
A
Giorda
R
R
Bresolin
N
N
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
D004268:DNA-Binding Proteins; D016189:Dystrophin; D012333:RNA, Messenger