A Landscape of Circadian and Ultradian Alternative Splicing Events in Mammalian Tissues

Abstract

Mounting evidence points to a role of the circadian clock in the temporal regulation of alternative splicing (AS). In this study, we carried out a systematic analysis of circadian and ultradian transcriptional rhythms to characterize the landscape of rhythmic AS events in 76 tissues from mouse and baboon. We found a bimodal phase distribution of splicing factors with 24-h rhythmic expression across tissues and species and identified putative oscillating AS events in murine tissues and pairs of differentially rhythmic splice isoforms of the same gene in baboon tissues that peaked at opposing times of the day. Genes with phase-shifted isoforms included oncogenes and tumor suppressors. We further explored these findings using a new circadian data-set of human colorectal cancer cell lines. Rhythmic isoform expression patterns differed between the primary tumor and the metastatic cell line, indicating a functional role of rhythmic AS that might be implicated in tumor progression.

Keywords: circadian rhythms, Ultradian Rhythms, Alternative splicing, splicing factors, splice isoforms, Cancer, tumor progression