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Poly(A) tail length regulates PABPC1 expression to tune translation in the heart.

ABSTRACT: The rate of protein synthesis in the adult heart is one of the lowest in mammalian tissues, but it increases substantially in response to stress and hypertrophic stimuli through largely obscure mechanisms. Here, we demonstrate that regulated expression of cytosolic poly(A)-binding protein 1 (PABPC1) modulates protein synthetic capacity of the mammalian heart. We uncover a poly(A) tail-based regulatory mechanism that dynamically controls PABPC1 protein synthesis in cardiomyocytes and thereby titrates cellular translation in response to developmental and hypertrophic cues. Our findings identify PABPC1 as a direct regulator of cardiac hypertrophy and define a new paradigm of gene regulation in the heart, where controlled changes in poly(A) tail length influence mRNA translation.

SUBMITTER: Chorghade S

PROVIDER: S-EPMC5487213 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Poly(A) tail length regulates PABPC1 expression to tune translation in the heart.

Chorghade Sandip S Seimetz Joseph J Emmons Russell R Yang Jing J Bresson Stefan M SM Lisio Michael De M Parise Gianni G Conrad Nicholas K NK Kalsotra Auinash A

eLife 20170627

The rate of protein synthesis in the adult heart is one of the lowest in mammalian tissues, but it increases substantially in response to stress and hypertrophic stimuli through largely obscure mechanisms. Here, we demonstrate that regulated expression of cytosolic poly(A)-binding protein 1 (PABPC1) modulates protein synthetic capacity of the mammalian heart. We uncover a poly(A) tail-based regulatory mechanism that dynamically controls PABPC1 protein synthesis in cardiomyocytes and thereby titr ...[more]

PMID: 28653618

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