A Role for LSM Genes in The Regulation of Circadian Rhythms in Plant And Human Cells

SOLEDAD PEREZ SANTANGELO; MARCELO J. YANOVSKY

Cordoba

Congreso; 16th International Congress on Photobiology; 2014

Circadian clocks allow organisms to time biological processes to the most appropriate phases of the day and year. We are interested in deciphering the regulatory networks that control clock function in plants, since this knowledge could be used to manipulate flowering time, a key factor influencing crop productivity. There is increasing evidence that propper regulation of clock function involves alterations in alternative splicing (AS) of clock genes, but little is known about the mechanisms linking AS and the clock. We have recently shown that defects in Protein Arginine Methyl Transferase 5, which transfers methyl groups to arginine residues present in Sm and LSm spliceosomal proteins, impair circadian rhythms in Arabidopsis. Here we show that some LSM genes, encoding core components of the spliceosomal U6 SnRNP complex, play a regulatory role in the control of circadian rhythms in plants and mammals. We found the circadian clock regulates expression of LSM5 in Arabidopsis plants and several LSM genes in mouse SCN. Further, mutations in LSM5 or LSM4 genes in Arabidopsis, or downregulation of LSM3, LSM5 or LSM7 expression in human cells, lengthens circadian period. Changes in expression and alternative splicing of some core-clock genes were identified in Arabidopsis lsm5 mutants, but the precise molecular mechanism causing period lengthening remains to be identified. Genome-wide expression analysis of either a weak lsm5 or a strong lsm4 mutant allele in Arabidopsis revealed larger effects on alternative compared to constitutive splicing. Remarkably, no significant defects were observed in the splicing of more than 95% of all introns evaluated using RNA-seq in the strong lsm4 mutant allele used in this study. These findings support the idea that some LSM genes play regulatory rather than constitutive roles in RNA processing, and that clock regulation of LSM gene expression is one mechanism integrating transcriptional and post-transcriptional regulatory layers within plant and mammalian circadian networks.