A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart

Author:

Anderson Douglas M.,Anderson Kelly M.,Nelson Benjamin R.,McAnally John R.,Bezprozvannaya Svetlana,Shelton John M.,Bassel-Duby Rhonda,Olson Eric N.ORCID

Abstract

Myocardin, a potent coactivator of serum response factor (SRF), competes with ternary complex factor (TCF) proteins for SRF binding to balance opposing mitogenic and myogenic gene programs in cardiac and smooth muscle. Here we identify a cardiac lncRNA transcribed adjacent to myocardin, named CARDINAL, which antagonizes SRF-dependent mitogenic gene transcription in the heart. CARDINAL-deficient mice show ectopic TCF/SRF-dependent mitogenic gene expression and decreased cardiac contractility in response to age and ischemic stress. CARDINAL forms a nuclear complex with SRF and inhibits TCF-mediated transactivation of the promitogenic gene c-fos, suggesting CARDINAL functions as an RNA cofactor for SRF in the heart.

Funder

National Institutes of Health

Fondation Leducq Networks of Excellence

Robert A. Welch Foundation

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

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