[Front Genet.]Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock

Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock Front Genet. 2021 Mar 26;12:656571. doi: 10.3389/fgene.2021.656571. eCollection 2021. Authors Yaling Wu 1 2 3 4 5 , Haijiao Zhao 5 , Eric Erquan Zhang 5 , Na Liu 1 2 3 4 5 Affiliations 1 Hubei Engineering Research Center of Special Wild Vegetables Breeding and Comprehensive Utilization Technology, Hubei Normal University, Huangshi, China. 2 Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, Hubei Normal University, Huangshi, China. 3 National Demonstration Center for Experimental Biology Education, Hubei Normal University, Huangshi, China. 4 College of Life Sciences, Hubei Normal University, Huangshi, China. 5 National Institute of Biological Sciences, Beijing, China. PMID: 33841513 PMCID: PMC8034388 DOI: 10.3389/fgene.2021.656571 Abstract The circadian clock governs our daily cycle of behavior and physiology. Previous studies have identified a handful of core clock components and hundreds of circadian modifiers. Here, we report the discovery that poly(C)-binding protein 1 (PCBP1), displaying a circadian expression pattern, was a novel circadian clock regulator. We found that knocking down PCBP1 resulted in period shortening in human U2OS cells, and that manipulations of PCBP1 expression altered the activity of CLOCK/BMAL1 in an E-box-based reporter assay. Further mechanistic study demonstrated that this clock function of PCBP1 appears to work by enhancing the association of Cryptochrome 1 (CRY1) with the CLOCK/BMAL1 complex, thereby negatively regulating the latter's activation. Co-immunoprecipitation of PCBP1 and core clock molecules confirmed the interactions between PCBP1 and CRY1, and a time-course qPCR assay revealed the rhythmic expression of PCBP1 in mouse hearts in vivo. Given that the RNA interference of mushroom-body expressed (mub), the poly(rC) binding protein (PCBP) homolog of Drosophila, in the clock neurons also led to a circadian phenotype in the locomotor assay, our study deemed PCBP1 a novel clock modifier whose circadian regulatory mechanism is conserved during evolution. Keywords: PCBP1; circadian clock; clock modifier; mechanism; period shortening. Copyright © 2021 Wu, Zhao, Zhang and Liu. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.