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

Genes Dev. 2021 Jun;35(11-12):835-840. doi: 10.1101/gad.348304.121. Epub 2021 May 13.

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: ELK-1; LINC00670; SRF; TCFs; c-Fos; long noncoding RNA; myocardin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Disease Models, Animal
  • Gene Deletion
  • Gene Expression Regulation / genetics*
  • Heart / physiology*
  • MEF2 Transcription Factors / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Contraction / genetics
  • Myocardial Infarction / genetics
  • Myocardial Infarction / physiopathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Serum Response Factor / genetics
  • Serum Response Factor / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation

Substances

  • MEF2 Transcription Factors
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Serum Response Factor
  • Trans-Activators
  • myocardin