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.posttranscriptional | alternative splicing | circadian clock | Arabidopsis | mammals C ircadian rhythms are persistent 24-h oscillations in biological processes that occur under constant environmental conditions. They allow organisms to coordinate multiple physiological processes with periodic or seasonal changes that occur in the environment. At the heart of the eukaryotic circadian system lies a complex set of interconnected transcriptional and translational feedback loops, in which a group of core clock genes regulate each other to ensure that their mRNA levels oscillate with a period of ∼24 h (1). The core oscillator in Arabidopsis thaliana involves two MYB domain-containing transcription factors, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), that repress the expression of TIMING OF CAB2 EXPRESSION 1 (TOC1) at the beginning of the day. In turn, TOC1, a member of the PSEUDO-RESPONSE REGULATOR (PRR) family, represses CCA1/LHY expression at the end of the day (2). Other clock components expressed throughout the day form multiple interconnected transcriptional feedback loops (2).Mounting evidence indicates that alternative splicing (AS), the process by which pre-mRNA molecules are differentially spliced to yield multiple mRNA isoforms from a single gene, plays a key role in the regulation of circadian networks in a variety of organisms, including Drosophila melanogaster (3), Neurospora crassa (4-6), and Arabidopsis (7-11). For example, the core clock genes period in Drosophila and frequency in Neurospora give rise to different mRNA isoforms through AS, which helps t...