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.

对细胞的机械刺激和机械转导在许多生物和病理过程中是必不可少的。糖皮质激素是一种重要的激素，其在细胞机械转导中的作用和机制仍然未知。在这里，我们报告糖皮质激素依赖于一种新型长链非编码 RNA (lncRNA) LINC01569来抵消细胞机械反应。此外，LINC01569通过破坏包括早期生长反应蛋白 1 ( EGR1 )、Cbp/P300 相互作用的反式激活因子 2 ( CITED2 ) 和糖皮质激素受体中的骨形态发生蛋白 7 ( BMP7 )在内的机械传感器的信使 RNA (mRNA) 来介导糖皮质激素对机械转导的影响–介导的 mRNA 衰变 (GMD) 方式。机械地，LINC01569直接与 GMD 因子 Y 盒结合蛋白 1 ( YBX1 ) 结合。然后，LINC01569-YBX1复合物通过特异性LINC01569 -mRNA相互作用被引导至EGR1、CITED2和BMP7的mRNA ，从而有助于GMD复合物的成功组装并触发GMD。我们的研究结果揭示了糖皮质激素在细胞机械转导和新型 lncRNA 依赖性 GMD 机制中的作用，并为早期干预机械障碍相关疾病提供了潜在策略。