Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA.

Transient transfection of the U1 snRNP 70K protein into COS cells induced nuclear reorganization and redistribution of the splicing factor SC-35, whereas hnRNP proteins were not affected. Correspondingly, splicing and nucleocytoplasmic transport of a coexpressed mRNA substrate was reduced by overexpression of U1-70K. The carboxy-terminal portion of U1-70K-encompassing repeats of Arg/Ser, Arg/Glu, and Arg/Asp localizes to the nucleus independently of U1 RNA and was responsible for these inhibitory effects. This region of U1-70K contains amino acid residues similar to those found in splicing factors SC-35, U2AF, su(wa), and in other SR proteins suggesting that U1-70K protein may serve as a focus of assembly for functional components of the splicing/transport machinery. These findings are compatible with models that propose that direct interaction between U1-70K and SR proteins play a regulatory role in early events of spliceosome assembly.