Identification and Characterization of Transcripts Regulated by Circadian Alternative Polyadenylation in Mouse Liver

dc.contributor.authorGendreau, Kerry L.en
dc.contributor.authorUnruh, Benjamin A.en
dc.contributor.authorZhou, Chuanlien
dc.contributor.authorKojima, Shihokoen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.description.abstractDynamic control of gene expression is a hallmark of the circadian system. In mouse liver, approximately 5-20% of RNAs are expressed rhythmically, and over 50% of mouse genes are rhythmically expressed in at least one tissue. Recent genome-wide analyses unveiled that, in addition to rhythmic transcription, various post-transcriptional mechanisms play crucial roles in driving rhythmic gene expression. Alternative polyadenylation (APA) is an emerging post-transcriptional mechanism that changes the 3-ends of transcripts by alternating poly(A) site usage. APA can thus result in changes in RNA processing, such as mRNA localization, stability, translation efficiency, and sometimes even in the localization of the encoded protein. It remains unclear, however, if and how APA is regulated by the circadian clock. To address this, we used an in silico approach and demonstrated in mouse liver that 57.4% of expressed genes undergo APA and each gene has 2.53 poly(A) sites on average. Among all expressed genes, 2.9% of genes alternate their poly(A) site usage with a circadian (i.e., approximately 24 hr) period. APA transcripts use distal sites with canonical poly(A) signals (PASs) more frequently; however, circadian APA transcripts exhibit less distinct usage preference between proximal and distal sites and use proximal sites more frequently. Circadian APA transcripts also harbor longer 3UTRs, making them more susceptible to post-transcriptional regulation. Overall, our study serves as a platform to ultimately understand the mechanisms of circadian APA regulation.en
dc.description.notesThe authors thank Ms. Naseem Maghzian and Ms. Connie Magarrelli for their technical assistance and Janet Webster for critical reading of the manuscript. This work was partially supported by a Grant for Basic Science Research Projects from the Sumitomo Foundation (to S.K.).en
dc.description.sponsorshipSumitomo Foundationen
dc.publisherGenetics Society of Americaen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.subjectcircadian rhythmsen
dc.subjectalternative polyadenylationen
dc.subjectin silicoen
dc.subjectmouse liveren
dc.titleIdentification and Characterization of Transcripts Regulated by Circadian Alternative Polyadenylation in Mouse Liveren
dc.title.serialG3-Genes Genomes Geneticsen
dc.typeArticle - Refereeden


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