A methyl transferase links the circadian clock to the regulation of alternative splicing

• Published in: Nature (London) Vol. 468; no. 7320; pp. 112 - 116
• Main Authors: Sanchez, Sabrina E., Petrillo, Ezequiel, Beckwith, Esteban J., Zhang, Xu, Rugnone, Matias L., Hernando, C. Esteban, Cuevas, Juan C., Godoy Herz, Micaela A., Depetris-Chauvin, Ana, Simpson, Craig G., Brown, John W. S., Cerdán, Pablo D., Borevitz, Justin O., Mas, Paloma, Ceriani, M. Fernanda, Kornblihtt, Alberto R., Yanovsky, Marcelo J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.11.2010; Nature Publishing Group
• Subjects: 631/337/1645/1946; 631/45/612/1238; 631/80/105; Alternative Splicing - genetics; Animals; Arabidopsis - enzymology; Arabidopsis - genetics; Arabidopsis - physiology; Arabidopsis - radiation effects; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; Arabidopsis thaliana; Arrays; Base Sequence; Biological and medical sciences; Circadian Clocks - genetics; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - genetics; Circadian Rhythm - physiology; Circadian rhythms; Darkness; Drosophila melanogaster; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila melanogaster - radiation effects; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Environmental changes; Environmental conditions; Epigenetics; Fourier transforms; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Plant; Genetic aspects; Humanities and Social Sciences; Insects; letter; Life Sciences; Light; Locomotor activity; Methylation; Methyltransferases; Molecular and cellular biology; Molecular genetics; multidisciplinary; Mutation; Neurons and Cognition; Other; Period Circadian Proteins - genetics; Phenotype; Physiological aspects; Protein Methyltransferases - genetics; Protein Methyltransferases - metabolism; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Proteins; RNA Precursors - genetics; RNA Precursors - metabolism; RNA Splice Sites - genetics; RNA splicing; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Science; Science (multidisciplinary); Spliceosomes - metabolism; Transcription Factors - genetics; Transcription. Transcription factor. Splicing. Rna processing; Argentina; Alternative splicing; Regulation(control); Biological rhythm; Circadian rhythm
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature09470

Time for some RNA editing Various biological processes are driven by the day/night cycle to occur at a certain time of day. One way the circadian system exerts these effects is through post-transcriptional regulation. Sanchez et al . show that PRMT5, a protein that transfers methyl groups onto subunits of the spliceosome — the complex that cuts non-protein-coding stretches from pre-RNA — is regulated by the light/dark cycle. This affects alternative splicing of some genes, making them subject to circadian control. This work shows one way by which the environment alters gene expression. Various biological processes are entrained by the day–night cycle to occur at a specific time of day. One way the circadian system exerts these effects is through post-transcriptional regulation. These authors show that a protein that transfers methyl groups onto several spliceosome subunits, PRMT5, is regulated by the light–dark cycle. Methylation of these subunits affects alternative splicing of some genes, thus making them subject to circadian control. Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day–night cycle 1 . Post-transcriptional regulation is emerging as an important component of circadian networks 2 , 3 , 4 , 5 , 6 , but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that PROTEIN ARGININE METHYL TRANSFERASE 5 (PRMT5), which transfers methyl groups to arginine residues present in histones 7 and Sm spliceosomal proteins 8 , 9 , links the circadian clock to the control of alternative splicing in plants. Mutations in PRMT5 impair several 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 ( PRR9 ). Furthermore, genome-wide studies show that PRMT5 contributes to the regulation of many pre-messenger-RNA splicing events, probably by modulating 5′-splice-site recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to the mediation of the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5-1 , a mutant affected in the Drosophila melanogaster PRMT5 homologue, and this is associated with alterations in splicing of the core-clock gene period and several clock-associated genes. Our results demonstrate a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.