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TDP43 depletion rescues aberrant CFTR exon 9 skipping
Author(s) -
Ayala Youhna M.,
Pagani Franco,
Baralle Francisco E.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.052
Subject(s) - rna splicing , exon , exon skipping , alternative splicing , rna , splice site mutation , exonic splicing enhancer , chemistry , microbiology and biotechnology , biology , gene , biochemistry
CFTR exon 9 presents a 3′ splice site polymorphism, (UG) m U 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) m U 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.