Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1

Transcription and mRNA processing are coupled events in vivo, but the mecha nisms that coordinate these processes are largely unknown. PGC-1 is a trans criptional coactivator that plays a major role in the regulation of adaptiv e thermogenesis. PGC-1 also has certain motifs characteristic of splicing f actors. We demonstrate here that mutations in the serine- and arginine-rich domain and RNA recognition motif of PGC-1 interfere with the ability of PG C-1 to induce mRNAs of target genes. These mutations also disrupt the abili ty of PGC-1 to co-localize and associate with RNA processing factors. PGC-1 can alter the processing of an mRNA, but only when it is loaded onto the p romoter of the gene. These data demonstrate the coordinated regulation of R NA transcription and processing through PGC-1.