Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1.
Transcription and mRNA processing are coupled events in vivo, but the mechanisms that coordinate these processes are largely unknown. PGC-1 is a transcriptional coactivator that plays a major role in the regulation of adaptive thermogenesis. PGC-1 also has certain motifs characteristic of splicing factors. We demonstrate here that mutations in the serine- and arginine-rich domain and RNA recognition motif of PGC-1 interfere with the ability of PGC-1 to induce mRNAs of target genes. These mutations also disrupt the ability 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 promoter of the gene. These data demonstrate the coordinated regulation of RNA transcription and processing through PGC-1.
Monsalve
M
M
Dana-Farber Cancer Institute and The Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wu
Z
Z
Adelmant
G
G
Puigserver
P
P
Fan
M
M
Spiegelman
B M
BM
D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine; D001833:Body Temperature Regulation; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D012694:Serine; D001120:Arginine