THE C-TERMINAL DOMAIN OF THE LARGEST SUBUNIT OF RNA-POLYMERASE-II INTERACTS WITH A NOVEL SET OF SERINE ARGININE-RICH PROTEINS/

Although transcription and pre-mRNA pro cessing are colocalized in euk aryotic nuclei, molecules linking these processes have not previously been described. We have identified four novel rat proteins by their ab ility to interact with the repetitive C-terminal domain (CTD) of RNA p olymerase II in a yeast two-hybrid assay. A yeast homolog of one of th e rat proteins has also been shown to interact with the CTD. These CTD -binding proteins are all similar to the SR (serine/arginine-rich) fam ily of proteins that have been shown to be involved in constitutive an d regulated splicing. In addition to alternating Ser-Arg domains, thes e proteins each contain discrete N-terminal or C-terminal CTD-binding domains. We have identified SR-related proteins in a complex that can be immunoprecipitated from nuclear extracts with antibodies directed a gainst RNA polymerase II. In addition, in vitro splicing is inhibited either by an antibody directed against the CTD or by wild-type but not mutant CTD peptides. Thus, these results suggest that the CTD and a s et of CTD-binding proteins may act to physically and functionally link transcription and pre-mRNA processing.