Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation

Abstract Uncovering the molecular basis of mammalian cardiomyocyte proliferation may eventually lead to better approaches for heart regeneration. Compared to extensively-studied transcriptional regulation, the roles of posttranscriptional regulation in cardiac cell fate decisions remain largely unkn...

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Autores principales:	Bingying Zhou, Junwei Liu, Zongna Ren, Fang Yao, Jingwei Ma, Jiangping Song, Brian Bennett, Yisong Zhen, Li Wang, Guang Hu, Shengshou Hu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b681699cad744c04b8dd4fa67ab9317c
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spelling	oai:doaj.org-article:b681699cad744c04b8dd4fa67ab9317c2021-12-02T15:05:14ZCnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation10.1038/s41598-017-01628-02045-2322https://doaj.org/article/b681699cad744c04b8dd4fa67ab9317c2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01628-0https://doaj.org/toc/2045-2322Abstract Uncovering the molecular basis of mammalian cardiomyocyte proliferation may eventually lead to better approaches for heart regeneration. Compared to extensively-studied transcriptional regulation, the roles of posttranscriptional regulation in cardiac cell fate decisions remain largely unknown. Here, we identified Cnot3 as a critical regulator in cardiomyocyte proliferation at the late stage of cardiac differentiation from human ESCs. Cnot3 was highly expressed in cardiomyocytes with higher proliferation potential in both human and mouse, and its depletion resulted in significant reduction in the proliferative capacity of cells. Furthermore, Cnot3 overexpression greatly enhanced proliferation in both cultured human cardiomyocytes and infarcted murine hearts. Mechanistically, the Ccr4-Not complex preferentially interacted with anti-proliferation gene transcripts in a Cnot3-dependent manner, and promoted their degradation. Together, our study supported the model that Cnot3 enhances cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation. It revealed a previously unrecognized role of mRNA degradation in cardiomyocyte growth, and suggested a potential strategy to control cardiac cell fates in development and diseases.Bingying ZhouJunwei LiuZongna RenFang YaoJingwei MaJiangping SongBrian BennettYisong ZhenLi WangGuang HuShengshou HuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bingying Zhou Junwei Liu Zongna Ren Fang Yao Jingwei Ma Jiangping Song Brian Bennett Yisong Zhen Li Wang Guang Hu Shengshou Hu Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
description	Abstract Uncovering the molecular basis of mammalian cardiomyocyte proliferation may eventually lead to better approaches for heart regeneration. Compared to extensively-studied transcriptional regulation, the roles of posttranscriptional regulation in cardiac cell fate decisions remain largely unknown. Here, we identified Cnot3 as a critical regulator in cardiomyocyte proliferation at the late stage of cardiac differentiation from human ESCs. Cnot3 was highly expressed in cardiomyocytes with higher proliferation potential in both human and mouse, and its depletion resulted in significant reduction in the proliferative capacity of cells. Furthermore, Cnot3 overexpression greatly enhanced proliferation in both cultured human cardiomyocytes and infarcted murine hearts. Mechanistically, the Ccr4-Not complex preferentially interacted with anti-proliferation gene transcripts in a Cnot3-dependent manner, and promoted their degradation. Together, our study supported the model that Cnot3 enhances cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation. It revealed a previously unrecognized role of mRNA degradation in cardiomyocyte growth, and suggested a potential strategy to control cardiac cell fates in development and diseases.
format	article
author	Bingying Zhou Junwei Liu Zongna Ren Fang Yao Jingwei Ma Jiangping Song Brian Bennett Yisong Zhen Li Wang Guang Hu Shengshou Hu
author_facet	Bingying Zhou Junwei Liu Zongna Ren Fang Yao Jingwei Ma Jiangping Song Brian Bennett Yisong Zhen Li Wang Guang Hu Shengshou Hu
author_sort	Bingying Zhou
title	Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
title_short	Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
title_full	Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
title_fullStr	Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
title_full_unstemmed	Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
title_sort	cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mrna degradation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b681699cad744c04b8dd4fa67ab9317c
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Cnot3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation

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