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

Abstract

Most living organisms have physiological and behavioral circadian rhythms controlled by molecular clocks. In mammals, several core clock genes show self-perpetuating oscillation profiles of their messenger RNAs (mRNAs) and proteins through anauto-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 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 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 forFubp1 in the molecular clock system.