Glucocorticoid counteracts cellular mechanoresponses by LINC01569-dependent glucocorticoid receptor-mediated mRNA decay.

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), <i>LINC01569</i> Further, <i>LINC01569</i> mediated glucocorticoid effects on mechanotransduction by destabilizing messenger RNA (mRNA) of mechanosensors including early growth response protein 1 (<i>EGR1</i>), Cbp/P300-interacting transactivator 2 (<i>CITED2</i>), and bone morphogenic protein 7 (<i>BMP7</i>) in glucocorticoid receptor-mediated mRNA decay (GMD) manner. Mechanistically, <i>LINC01569</i> directly bound to the GMD factor Y-box-binding protein 1 (<i>YBX1</i>). Then, the <i>LINC01569-YBX1</i> complex was guided to the mRNAs of <i>EGR1</i>, <i>CITED2</i>, and <i>BMP7</i> through specific <i>LINC01569</i>-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.