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 an 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 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 for Fubp1 in the molecular clock system.

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

“…When it is abnormal, the resulting changes to the normal rhythm of cell proliferation lead to the occurrence of tumors. PER1 has a role in feeding and active behavior in mammals and is controlled by circadian rhythms (Kim et al, 2020). From a non-tumor perspective, PER1 is related to conditions such as Parkinson's disease, obesity, sleep, drug resistance, and premature ovarian insufficiency (Zheng et al, 2019;Delgado-Lara et al, 2020;EmeklI et al, 2020;Mabrouk et al, 2020;Arellanes-Licea et al, 2021).…”

A novel antisense lncRNA NT5E promotes progression by modulating the expression of SYNCRIP and predicts a poor prognosis in pancreatic cancer

“…A recent study reported that, based on utilizing the publicly available gene expression data set and ChIP results, the transcription factor Fubp1 can bind to the promoter region of SYNCRIP and promote its transcription. 43 Furthermore, it was reported that Fubp1 can form an RNA-protein complex with lncRNA. 44 Accordingly, we speculated that lncNT5E might recruit Fubp1 to regulate SYNCRIP expression.…”

“…There were few literature regarding transcription factors or regulatory complexes related to SYNCRIP. A recent study reported that, based on utilizing the publicly available gene expression data set and ChIP results, the transcription factor Fubp1 can bind to the promoter region of SYNCRIP and promote its transcription 43 . Furthermore, it was reported that Fubp1 can form an RNA‐protein complex with lncRNA 44 .…”