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

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

doi:10.1101/gad.348304.121

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

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

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1-6
Number of pages	6
Journal	Genes and Development
Volume	38
Issue number	11-12
DOIs	https://doi.org/10.1101/gad.348304.121
State	Published - Jun 1 2021

Keywords

C-Fos
ELK-1
LINC00670
Long noncoding RNA
Myocardin
SRF
TCFs

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.348304.121

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title = "A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart",

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.",

keywords = "C-Fos, ELK-1, LINC00670, Long noncoding RNA, Myocardin, SRF, TCFs",

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AU - Anderson, Douglas M.

AU - Anderson, Kelly M.

AU - Nelson, Benjamin R.

AU - McAnally, John R.

AU - Bezprozvannaya, Svetlana

AU - Shelton, John M.

AU - Bassel-Duby, Rhonda

AU - Olson, Eric N.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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.

AB - 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.

KW - C-Fos

KW - ELK-1

KW - LINC00670

KW - Long noncoding RNA

KW - Myocardin

KW - SRF

KW - TCFs

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JO - Genes and Development

JF - Genes and Development

IS - 11-12

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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