title: Role for LSM genes in the regulation of circadian rhythms.
abstract: Growing evidence suggests that core spliceosomal components differentially affect RNA processing of specific genes; however, whether changes in the levels or activities of these factors control specific signaling pathways is largely unknown. Here we show that some SM-like (LSM) genes, which encode core components of the spliceosomal U6 small nuclear ribonucleoprotein complex, regulate circadian rhythms in plants and mammals. We found that the circadian clock regulates the expression of LSM5 in Arabidopsis plants and several LSM genes in mouse suprachiasmatic nucleus. Further, mutations in LSM5 or LSM4 in Arabidopsis, or down-regulation of LSM3, LSM5, or LSM7 expression in human cells, lengthens the circadian period. Although we identified changes in the expression and alternative splicing of some core clock genes in Arabidopsis lsm5 mutants, 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 splicing than on constitutive splicing. Remarkably, large splicing defects were not observed in most of the 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 both regulatory and constitutive roles in RNA processing, contributing to the fine-tuning of specific signaling pathways.
authors.affiliation: Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, C1405BWE, Buenos Aires, Argentina; and.
authors.forename: Soledad
authors.initials: S
authors.lastname: Perez-Santángelo
authors.affiliation: Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, C1405BWE, Buenos Aires, Argentina; and.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Mancini
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Francey
authors.affiliation: Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, C1405BWE, Buenos Aires, Argentina; and.
authors.forename: Ruben Gustavo
authors.initials: RG
authors.lastname: Schlaen
authors.affiliation: Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, C1405BWE, Buenos Aires, Argentina; and.
authors.forename: Ariel
authors.initials: A
authors.lastname: Chernomoretz
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: John B
authors.initials: JB
authors.lastname: Hogenesch
authors.affiliation: Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, C1405BWE, Buenos Aires, Argentina; and myanovsky@leloir.org.ar.
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Yanovsky
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D017360:Arabidopsis / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002940:Circadian Rhythm; D018506:Gene Expression Regulation, Plant; D023281:Genomics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D018515:Plant Leaves / Q000378:metabolism; D010940:Plant Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000502:physiology*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D017381:Spliceosomes / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D010940:Plant Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; C443479:sad1 protein, Arabidopsis
keywords: Arabidopsis; alternative splicing; circadian clock; mammals; posttranscriptional