A physical and functional link between splicing factors promotes pre-mRNA 3' end processing.

Polypyrimidine tract-binding protein (PTB) is a splicing regulator that also plays a positive role in pre-mRNA 3' end processing when bound upstream of the polyadenylation signal (pA signal). Here, we address the mechanism of PTB stimulatory function in mRNA 3' end formation. We identify PTB as the protein factor whose binding to the human beta-globin (HBB) 3' UTR is abrogated by a 3' end processing-inactivating mutation.

The c.5242C>A BRCA1 missense variant induces exon skipping by increasing splicing repressors binding.

Several unclassified variants (UV) of BRCA1 can be deleterious by affecting normal pre-mRNA splicing. Here, we investigated the consequences at the mRNA level of the frequently encountered c.5242C>A UV in BRCA1 exon 18.

Pharmacological-based translational induction of transgene expression in mammalian cells.

In the quest for the development of pharmacological switches that control gene expression, no system has been reported that regulates at the translational level. To permit small-molecule control of transgene translation, we have constructed a farnesyl transferase inhibitor-responsive translation initiation factor. This artificial protein is a three-component chimaera consisting of the ribosome recruitment core of the eIF4G1 eukaryotic translation initiation factor, the RNA-binding domain of the R17 bacteriophage coat protein and the plasma membrane localization CAAX motif of farnesylated H-Ras.