Glucocorticoid counteracts cellular mechanoresponses by LINC01569-dependent glucocorticoid receptor–mediated mRNA decay
Open Access
- 26 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (9), eabd9923
- https://doi.org/10.1126/sciadv.abd9923
Abstract
Mechanical stimuli on cells and mechanotransduction are essential in many biological and pathological processes. Glucocorticoid is an important hormone, roles, and mechanisms of which in cellular mechanotransduction remain unknown. Here, we report that glucocorticoid counteracted cellular mechanoresponses dependently on a novel long noncoding RNA (lncRNA), LINC01569. Further, LINC01569 mediated glucocorticoid effects on mechanotransduction by destabilizing messenger RNA (mRNA) of mechanosensors including early growth response protein 1 (EGR1), Cbp/P300-interacting transactivator 2 (CITED2), and bone morphogenic protein 7 (BMP7) in glucocorticoid receptor–mediated mRNA decay (GMD) manner. Mechanistically, LINC01569 directly bound to the GMD factor Y-box–binding protein 1 (YBX1). Then, the LINC01569-YBX1 complex was guided to the mRNAs of EGR1, CITED2, and BMP7 through specific LINC01569-mRNA interaction, thereby contributing to the successful assembly of GMD complex and triggering GMD. Our results uncovered roles of glucocorticoid in cellular mechanotransduction and novel lncRNA-dependent GMD machinery and provided potential strategy for early intervention in mechanical disorder–associated diseases.Funding Information
- National Natural Science Foundation of China (81702554)
- National Natural Science Foundation of China (81971834)
- National Natural Science Foundation of China (81802661)
- National Natural Science Foundation of China (81772071)
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