Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3 processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3 processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PAS). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is modulated by phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like regions in regulatory and core factors may provide a common activation mechanism for mRNA 3 processing, splicing, and potentially other steps in RNA metabolism. SOURCE: Elmira ForouzmandShi lab University of California Irvine

Pluto Bioinformatics

GSE101871: A unified activation mechanism for mRNA 3 end processing and splicing mediated by SR superfamily proteins