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

• DOI: 10.7554/elife.24139
• Publication Date: 2017-06-27T00:00:27Z
• Authors: Sandip Chorghade; Joseph Seimetz; Russell Emmons; Jing Yang; Stefan M Bresson; Michael De Lisio; Gianni Parise; Nicholas K Conrad; Auinash Kalsotra
• Keywords: translation control; 0301 basic medicine; protein synthesis; QH301-705.5; cardiac hypertrophy; Science; Myocardium; Q; R; Biochemistry; Poly(A)-Binding Protein I; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; postnatal heart development; Gene Expression Regulation; Protein Biosynthesis; Medicine; Animals; Humans; post-transcriptional gene regulation; RNA, Messenger; polyadenylation; Biology (General)

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.