Available online

rin r), modules consisting of tandem RNA recognition motifs (RRMs; RRM1– The splicing of precursor mRNA (pre-mRNA) is family of splicing cofactors are the SR proteins doi:10.1016/j.jmb.2008.07.055 Available online at wwwessential for proteome diversity and many cellular regulatory processes, but is also associated with numerous diseases when mistakes are propagated into themature splicedmRNA.1–4 Splicing occurs in a macromolecular complex known as the spliceosome, (splicing factors containing arginine-serine repeats), so named because they contain a C-terminal domain composed largely of arginine-serine dipeptide repeats (RS domain, a domain rich in arginine-serine repeats). In addition to these repetitive sequences, SR proteins contain one or two N-terminal RNA recognition motifs (RRMs) that are essential for recognition of exonic enhancer sequences in pre-mRNA.6–8 The SR proteins play roles in both constitutive and alternative splicing.9,10 While SR proteins are critical for the earl