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Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock

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 nove...

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Detalles Bibliográficos
Autores principales: Wu, Yaling, Zhao, Haijiao, Zhang, Eric Erquan, Liu, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034388/
https://www.ncbi.nlm.nih.gov/pubmed/33841513
http://dx.doi.org/10.3389/fgene.2021.656571
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author Wu, Yaling
Zhao, Haijiao
Zhang, Eric Erquan
Liu, Na
author_facet Wu, Yaling
Zhao, Haijiao
Zhang, Eric Erquan
Liu, Na
author_sort Wu, Yaling
collection PubMed
description 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.
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spelling pubmed-80343882021-04-10 Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock Wu, Yaling Zhao, Haijiao Zhang, Eric Erquan Liu, Na Front Genet Genetics 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. Frontiers Media S.A. 2021-03-26 /pmc/articles/PMC8034388/ /pubmed/33841513 http://dx.doi.org/10.3389/fgene.2021.656571 Text en Copyright © 2021 Wu, Zhao, Zhang and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wu, Yaling
Zhao, Haijiao
Zhang, Eric Erquan
Liu, Na
Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock
title Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock
title_full Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock
title_fullStr Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock
title_full_unstemmed Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock
title_short Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock
title_sort identification of pcbp1 as a novel modulator of mammalian circadian clock
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034388/
https://www.ncbi.nlm.nih.gov/pubmed/33841513
http://dx.doi.org/10.3389/fgene.2021.656571
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