title: TDP43 depletion rescues aberrant CFTR exon 9 skipping.
abstract: CFTR exon 9 presents a 3' splice site polymorphism, (UG)mU(n), whose composition influences splicing. TDP43 specifically binds the UG tract of the transcript and inhibits splicing in vitro. We report that depletion of TDP43 through RNA interference removes splicing inhibition caused by unfavorable (UG)mU(n) sequences, indicating that TDP43 exerts a potent inhibitory effect in vivo. We also show that the UG-TDP43 interaction has a dominant role over other exon 9 splicing regulatory elements. These results suggest that TDP43 association near a splice site has determined the evolution of positive splicing regulatory elements to contrast this inhibition.
authors.affiliation: Department of Molecular Pathology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34012 Trieste, Italy.
authors.forename: Youhna M
authors.initials: YM
authors.lastname: Ayala
authors.forename: Franco
authors.initials: F
authors.lastname: Pagani
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
mesh_terms: D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D022821:RNA Splice Sites / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D050436:Regulatory Elements, Transcriptional; D017384:Sequence Deletion; D014162:Transfection
chemical_list: C505032:CFTR protein, human; D004268:DNA-Binding Proteins; D022821:RNA Splice Sites; D034741:RNA, Small Interfering; D019005:Cystic Fibrosis Transmembrane Conductance Regulator