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

Sandip Chorghade, Joseph Seimetz, Russell Emmons, Jing Yang, Stefan M. Bresson, Michael de Lisio, Gianni Parise, Nicholas K. Conrad, Auinash Kalsotra

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Article numbere24139
JournaleLife
Volume6
DOIs
StatePublished - Jun 27 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Chorghade, S., Seimetz, J., Emmons, R., Yang, J., Bresson, S. M., de Lisio, M., Parise, G., Conrad, N. K., & Kalsotra, A. (2017). Poly(A) tail length regulates PABPC1 expression to tune translation in the heart. eLife, 6, [e24139]. https://doi.org/10.7554/eLife.24139