Distinct Binding Specificities and Functions of Higher Eukaryotic Polypyrimidine Tract-Binding Proteins | CU Experts

; In higher eukaryotes, the polypyrimidine-tract (Py-tract) adjacent to the 3′ splice site is recognized by several proteins, including the essential splicing factor U2AF; 65; , the splicing regulator Sex-lethal (Sxl), and polypyrimidine tract-binding protein (PTB), whose function is unknown. Iterative in vitro genetic selection was used to show that these proteins have distinct sequence preferences. The uridine-rich degenerate sequences selected by U2AF; 65; are similar to those present in the diverse array of natural metazoan Py-tracts. In contrast, the Sxl-consensus is a highly specific sequence, which can help explain the ability of Sxl to regulate splicing of; transformer; pre-mRNA and autoregulate splicing of its own pre-mRNA. The PTB-consensus is not a typical Py-tract; it can be found in certain alternatively spliced pre-mRNAs that undergo negative regulation. Here it is shown that PTB can regulate alternative splicing by selectively repressing 3′ splice sites that contain a PTB-binding site.;

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