PRMT5, a Piece Connecting the Circadian Clock and Alternative Splicing

SABRINA E. SANCHEZ; EZEQUIEL PETRILLO; XU ZHANG; MATIAS L. RUGNONE; C. ESTEBAN HERNANDO; MICAELA A. GODOY HERZ; CRAIG G. SIMPSON; JOHN W.S. BROWN; JUSTIN O. BOREVITZ; PALOMA MAS; ALBERTO R. KORNBLIHTT; MARCELO J. YANOVSKY

Madison

Conferencia; 22nd International Conference on Arabidopsis Research; 2011

Circadian clocks are endogenous mechanisms that allow organisms to adjust and to anticipate physiological and developmental responses to environmental changes. Transcriptional and posttranslational processes are known to be crucial regulatory steps for proper functioning of biological rhythms. Alternative splicing is a process that generates multiple mRNA products from a single gene enhancing proteome diversity. Until now, several examples of co-regulation of these mechanisms have been demonstrated in different organisms, but a direct link was missing. We have conducted a genetic screen using Arabidopsis thaliana as a model system to identify novel components of the circadian signaling network and we isolated a new mutant allele of the PRMT5 gene, which encodes for an arginine methyltransferase. Analysis of prmt5, a long period mutant, allowed us to determine that PRMT5 is involved in the proper functioning of the central core of the circadian clock and that PRMT5 expression follows itself a circadian pattern, suggesting that it is part of a feedback loop controlling clock function. We also found that PRMT5 is responsible for alternative splicing defects detected in the mutant plants and it modulates the recognition of donor or 5? splice sites, being specially important for the weak ones. Moreover, this protein seems to be, at least in part, the link between alternative splicing and the circadian network. This connection seems to have physiological relevance, since Rubisco Activase alternative splicing is regulated both by the circadian clock and PRMT5. Finally, we detected an altered photomorphogenic development in the mutant, suggesting a defect in light perception or signaling. These data suggest that PRMT5 could be a useful tool to fine-tuning the timing and place of expression of different gene targets and would be the first example identified of a protein linking circadian clocks to alternative splicing.