CRISPR/Cas-mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein via downregulating Syncrip expression.

Most living organisms have the physiological and behavioral circadian rhythms controlled by the molecular clocks. In mammals, several core clock genes show the self-perpetuating oscillation profiles of their mRNAs and proteins through the auto-regulatory transcription-translation feedback loop (TTFL). As a critical component in the molecular clock system, Period 1 (Per1) contributes to the maintenance of circadian rhythm duration predominantly in peripheral clocks. Alterations in Per1 expression and oscillating patterns lead to the development of cancers as well as the circadian rhythm abnormalities. In this study, we demonstrate that the phasic profile of Per1 protein was clearly disrupted in CRISPR/Cas-mediated Fubp1-deficient cells. Although Fubp1 does not show the rhythmic expression, Fubp1 upregulates the mRNA and protein level of Syncrip, the main post-transcriptional regulator of Per1 protein oscillation. In addition to the diverse physiological functions of Fubp1, including cell cycle regulation and cellular metabolic control, our results suggest new roles of Fubp1 in molecular clock system. This article is protected by copyright. All rights reserved.