IFEVA   02662
INSTITUTO DE INVESTIGACIONES FISIOLOGICAS Y ECOLOGICAS VINCULADAS A LA AGRICULTURA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Protein arginine methyl transferase 5 links the circadian clock to the regulation of alternative splicing
Autor/es:
SABRINA E. SANCHEZ; EZEQUIEL PETRILLO; ESTEBAN HERNANDO; MATIAS RUGNONE; XU ZHANG; JUSTIN BOREVITZ; ESTEBAN BECKWITH; CRAIG SIMPSON; JOHN BROWN; FERNANDA CERIANI; PABLO CERDÁN; ALBERTO KORNBLIHTT; PALOMA MAS; MARCELO J. YANOVSKY
Lugar:
Sandestin, Florida, USA.
Reunión:
Congreso; Society for Research on Biological Rhythms, 12th Biennial Meeting; 2010
Resumen:
Protein arginine methyltransferase 5 (PRMT5) symmetrically methylates histone and non-histone proteins, such as spliceosomal Sm-proteins. Although a role for PRMT5 in the epigenetic regulation of gene expression is well known, whether and how PRMT5 affects splicing remains uncertain. Here we show that mutations in prmt5 lengthened the period of multiple circadian rhythms in Arabidopsis. The circadian phenotype of the mutant was associated with defective regulation of alternative splicing of the central clock gene PRR9, and we show that functional PRR9 and PRR7 genes are required for PRMT5 effects on circadian period. PRMT5 also contributed to the regulation of circadian rhythms of locomotor behavior and appropriate splicing of clock associated genes such as period, takeout and norpA in Drosophila. Genome wide analysis using Affymetrix tiling arrays revealed alterations in alternative splicing regulation spread throughout the genome, but restricted to a few hundred genes in Arabidopsis and Drosophila. In particular, PRMT5 effects were associated with defective recognition of a subset of donor splice sites. Our results are in agreement with a previous hypothesis suggesting that the C-terminal region of Sm spliceosomal proteins, which is the region where Arg methylation by PRMT5 activity takes place, contributes to 5´splice site (5´ss) recognition stabilizing weak RNA-RNA interactions between 5´ss of pre-mRNAs and the 5´end of U1snRNA.  We propose that PRMT5 has been recruited independently in plants and flies to regulate the circadian network given its key ability to modulate many physiological processes acting as an epigenetic regulator of gene expression, and as a master regulator of alternative splicing.