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The polypyrimidine tract binding protein (PTB) prevents the activity of an intronic regulatory element that promotes the usage of a composite 3' terminal exon

Authors: 
Anquetil V, Le Sommer C, Méreau A, Hamon S, Lerivray H, Hardy S
Citation: 
J Biol Chem. 2009 Sep 17. [Epub ahead of print]
Abstract: 
Alternative splicing of 3' terminal exons plays a critical role in gene expression by producing mRNA with distinct 3' untranslated regions (UTR) that regulate their fate and their expression. The Xenopus alpha-tropomyosin pre-mRNA possesses a composite internal/3' terminal exon (exon 9A9') that is differentially processed depending on the embryonic tissue. Exon 9A9' is repressed in non muscle tissue by the polypyrimidine tract binding protein (PTB) whereas it is selected as a 3' terminal or internal exon in myotomal cells and adult striated muscles respectively. We report here the identification of an intronic regulatory element, designated UTE (Upstream Terminal exon Enhancer), that is required for the specific usage of exon 9A9' as a 3' terminal exon in the myotome. We demonstrate that PTB prevents the activity of UTE in non muscle cells while a sub-class of SR proteins promotes the selection of exon 9A9' in a UTE dependant way. Morpholino targeted blocking of UTE in the embryo, strongly reduced the inclusion of exon 9A9' as a 3' terminal exon in the endogenous mRNA, demonstrating the function of UTE under physiological circumstances. This strategy allowed us to reveal a splicing pathway that generates a mRNA with no in frame stop codon and whose steady state level is translation dependant. This result suggests that a nonstop decay (NSD) mechanism participates to the strict control of the 3' end processing of the alpha-tropomyosin pre-mRNA.
Epub: 
Not Epub
Organism or Cell Type: 
Xenopus