The processing of messenger RNA precursors (pre-mRNA) to mRNA in metazoans requires a large number of proteins that contain domains rich in alternating arginine and serine residues (RS domains). These include members of the SR family of splicing factors and proteins that are structurally and functionally distinct from the SR family, collectively referred to below as SR-related proteins. Both groups of RS domain proteins function in constitutive and regulated pre-mRNA splicing. Recently, several SR-related proteins have been identified that are associated with the transcriptional machinery. Other SR-related proteins are associated with mRNA 3' end formation and have been implicated in export. We review these findings and evidence that proteins containing RS domains may play a fundamental role in coordinating different steps in the synthesis and processing of pre-mRNA.