ALTERNATIVE SPLICING MODULATION BY PRMT5 AND A POSSIBLE INTERACTION WITH miRNA PRODUCTION

EZEQUIEL PETRILLO; SABRINA SANCHEZ; MICAELA A. GODOY HERZ; MARCELO JAVIER YANOVSKY; ALBERTO R. KORNBLIHTT

Congreso; SAIB - XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day/night cycle. PROTEIN ARGININE METHYL TRANSFERASE 5 (PRMT5), which transfers methyl groups to arginine residues present in histones and Sm spliceosomal proteins, links the circadian clock to the control of alternative splicing in plants. We found that mutations in PRMT5 impair multiple circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9. Furthermore, genome wide studies show that PRMT5 contributes to regulate many pre-mRNA splicing events most likely modulating 5´splice site recognition. Among the altered alternative splicing events, we detected an inhibition of splice variants accumulation of the npcRNA78 gene that contains the miR162a sequence in an alternative intron. This miRNA targets and produces the cleavage of the Dicer Like-1 (DCL1) mRNA, which is the responsible enzyme of miRNA production in Arabidopsis thaliana. With the aim of understanding the interaction between the splicing process and the DCL1-catalyzed miRNA production, we will evaluate whether the npcRNA78's splicing inhibition in the prmt5 mutant leads to an over-accumulation of miR162a and whether this fact could cause an unbalance in global miRNA production.