A methyl transferase links alternative splicing to the circadian clock

SANCHEZ, SE; PETRILLO, E; BECKWITH, E; ZHANG, X; RUGNONE, ML; HERNANDO, CE; GODOY-HERZ, M; DEPETRIS-CHAUVIN, A; CERDAN, PD; BROWN, JWS; BOREVITZ, J; MAS, P; CERIANI, MF; KORNBLIHTT, A; YANOVSKY, MJ

NATURE

NATURE PUBLISHING GROUP

Año: 2010

0028-0836

Circadian rhythms allow organisms to time biological processes to the mostappropriate phases of the day/night cycle1. Post-transcriptional regulation isemerging as an important component of circadian networks2-6, but the molecularmechanisms linking the circadian clock to the control of RNA processing arelargely unknown. Here we show that Protein Arginine Methyl Transferase 5(PRMT5), which transfers methyl groups to arginine residues present in histones7and Sm spliceosomal proteins8,9, links the circadian clock to the control ofalternative splicing in plants. Mutations in prmt5 impair multiple circadianrhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by astrong alteration in alternative splicing of the core-clock gene PSEUDORESPONSE REGULATOR 9 (PRR9). Furthermore, genome wide studies show thatPRMT5 contributes to regulate many pre-mRNA splicing events most likelymodulating 5´splice site (5´ss) recognition. PRMT5 expression shows daily andcircadian oscillations, and this contributes to mediate the circadian regulation ofexpression and alternative splicing of a subset of genes. Circadian rhythms inlocomotor activity are also disrupted in dart5, a mutant affected in the Drosophilamelanogaster PRMT5 homolog, and this is associated with alterations in splicing ofthe core-clock gene period (per) and several clock associated genes. Our resultsreveal a key role for PRMT5 in the regulation of alternative splicing and indicatethat the interplay between the circadian clock and the regulation of alternativesplicing by PRMT5 constitutes a common mechanism that helps organisms tosynchronize physiological processes with daily changes in environmentalconditions.