Protein arginine methyl transferase 5 links the circadian clock to the regulation of alternative splicing

SABRINA E. SANCHEZ; EZEQUIEL PETRILLO; ESTEBAN J. BECKWITH; ESTEBAN HERNANDO; MATÍAS L. RUGNONE; XU ZHANG; JUSTIN O. BOREVITZ; CRAIG SIMPSON; JOHN BROWN; PABLO D. CERDÁN; PALOMA MAS; M. FERNANDA CERIANI; ALBERTO R. KORNBLIHTT; MARCELO J. YANOVSKY

Destin

Congreso; 12th Biennial Meeting Society for Research on Biological Rhythms; 2010

Society for Research on Biological Rhythms

Post-transcriptional regulation is emerging as an important component of circadian networks ineukaryotic organisms, but the molecular mechanisms linking the circadian clock to the control of RNAprocessing are largely unknown. Here we show that Protein Arginine Methyl Transferase 5 (PRMT5),which transfers methyl groups to arginine residues present in Sm spliceosomal proteins, links thecircadian clock to the control of alternative splicing in plants and flies. Mutations in prmt5 impairmultiple circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, bya strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9(PRR9). Furthermore, genome wide studies show that PRMT5 contributes to regulate many pre-mRNAsplicing events, and reveal an important role for PRMT5 in the control of alternative splicing. PRMT5130 SRBR 2010 program and abstractsexpression shows diurnal and circadian oscillations, suggesting it could link the circadian clock tothe regulation of alternative splicing. Indeed, PRMT5 contributes to modulate rhythms in alternativesplicing of RUBISCO ACTIVASE that optimize photosynthesis to daily changes in light conditions. We also show that circadian rhythms in locomotor activity are disrupted in dart5, a mutant affected inthe Drosophila melanogaster PRMT5 homolog, and this is associated with a dramatic alteration inthe circadian pattern of alternative splicing of the core-clock gene period (per). Our results indicatethat the interplay between the circadian clock and the regulation of alternative splicing mediated byPRMT5 constitutes a novel mechanism that helps organisms to synchronize physiological processeswith daily changes in environmental conditions.