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. Author manuscript; available in PMC: 2018 Sep 1.
Published in final edited form as: Circ Res. 2017 Sep 1;121(6):591–593. doi: 10.1161/CIRCRESAHA.117.311722

Figure.

Figure

In addition to the established direct role of SRF, myocardin, and other transcriptional activators and repressors on SMC contractile gene expression (bottom right3), levels of the contractile protein, αSMA, are fine-tuned through the activity of a TGFβ / NRG-1-ICD / circActa2 / miR-548f-5p axis. TGFβ stimulates NRG1 expression and cleavage, promoting nuclear translocation of NRG-1-ICD. Nuclear NRG-1-ICD recruits Ikzf1 and forms a stable transcriptional complex that interacts with the first intron of the Acta2 gene inducing circActa2 formation. circActa2 functions as a miRNA “sponge,” interacting with and repressing miR-548f-59, which targets αSMA mRNA for degradation, thereby resulting in increased αSMA levels and enhanced SMC contractile function. NRG-1, neuregulin-1; NRG-1-ICD, neuregulin-1 intracellular domain; circActa2, circular RNA Acta2; TGFβ, transforming growth factor-β; SRF, serum response factor; MyoCD, myocardin; miR-548f-5p, microRNA-548f-5p; αSMA, smooth muscle alpha actin (Acta2).