Brain cytoplasmic RNA 1 suppresses smooth muscle differentiation and vascular development in mice

The Journal of Biological Chemistry
Yung-Chun WangShi-You Chen

Abstract

The cardiovascular system develops during the early stages of embryogenesis, and differentiation of smooth muscle cells (SMCs) is essential for that process. SMC differentiation is critically regulated by transforming growth factor (TGF)-β/SMAD family member 3 (SMAD3) signaling, but other regulators may also play a role. For example, long noncoding RNAs (lncRNAs) regulate various cellular activities and events, such as proliferation, differentiation, and apoptosis. However, whether long noncoding RNAs also regulate SMC differentiation remains largely unknown. Here, using the murine cell line C3H10T1/2, we found that brain cytoplasmic RNA 1 (BC1) is an important regulator of SMC differentiation. BC1 overexpression suppressed, whereas BC1 knockdown promoted, TGF-β-induced SMC differentiation, as indicated by altered cell morphology and expression of multiple SMC markers, including smooth muscle α-actin (αSMA), calponin, and smooth muscle 22α (SM22α). BC1 appeared to block SMAD3 activity and inhibit SMC marker gene transcription. Mechanistically, BC1 bound to SMAD3 via RNA SMAD-binding elements (rSBEs) and thus impeded TGF-β-induced SMAD3 translocation to the nucleus. This prevented SMAD3 from binding to SBEs in SMC marker gene pr...Continue Reading

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Citations

Apr 20, 2018·Alcoholism, Clinical and Experimental Research·Anna N Bukiya, Alex M Dopico
Feb 23, 2019·Cell Death & Disease·Yutong SuiGuangyu Li
Apr 30, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Yung-Chun WangShi-You Chen

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