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.

中文翻译：

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与心肌素相邻的 lncRNA 平衡心脏中 SRF 依赖性基因转录

心肌素是一种有效的血清反应因子 (SRF) 共激活剂，与三元复合因子 (TCF) 蛋白竞争 SRF 结合，以平衡心肌和平滑肌中相反的促有丝分裂和生肌基因程序。在这里，我们鉴定了一种与心肌蛋白相邻转录的心脏 lncRNA ，命名为 CARDINAL，它可以拮抗心脏中 SRF 依赖性有丝分裂基因的转录。CARDINAL缺陷小鼠显示异位 TCF/SRF 依赖性有丝分裂基因表达和心脏收缩力降低以响应年龄和缺血应激。CARDINAL 与 SRF 形成核复合物并抑制 TCF 介导的促有丝分裂基因 c-fos 的反式激活，这表明 CARDINAL 作为心脏中 SRF 的 RNA 辅因子发挥作用。