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 journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalGenes and Development
Volume38
Issue number11-12
DOIs
StatePublished - 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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