ARGININE SERINE-RICH DOMAINS OF SR PROTEINS CAN FUNCTION AS ACTIVATORS OF PRE-MESSENGER-RNA SPLICING/

Serine/arginine (SR)-rich splicing factors contain an RNA binding doma in and an arginine/serine (RS)-rich domain required for protein-protei n interactions. In addition to their roles in the basic splicing react ion, SR proteins function as components of splicing enhancer complexes . Here, we investigate the role of RS domains in splicing enhancer fun ction. Hybrid proteins containing RS domains fused to the MS2 RNA bind ing protein were tested in vitro with RNA substrates bearing an MS2 re cognition sequence. These hybrid proteins activated splicing in nuclea r extracts, but not in S100 extracts lacking SR proteins. However, int act recombinant SR proteins could complement the activity of the hybri d proteins in S100 extracts. These data demonstrate that RS domains fu nction as splicing activators and suggest that the general and enhance r-dependent functions of SR proteins can be uncoupled.