Biological Environmental Science and Engineering Division, KAUST Environmental Epigenetics Program, King Abdullah University of Science and Technology (KAUST), 4700 KAUST, Thuwal, 23955-6900, Saudi Arabia.
Sequentia Biotech, Carrer Comte D'Urgell 240, Barcelona, 08036, Spain.
Cell Death Dis. 2021 Sep 16;12(10):850. doi: 10.1038/s41419-021-04082-z.
PRC2-mediated epigenetic function involves the interaction with long non-coding RNAs (lncRNAs). Although the identity of some of these RNAs has been elucidated in the context of developmental programs, their counterparts in postmitotic adult tissue homeostasis remain uncharacterized. To this aim, we used terminally differentiated postmitotic skeletal muscle cells in which oxidative stress induces the dynamic activation of PRC2-Ezh1 through Embryonic Ectoderm Develpment (EED) shuttling to the nucleus. We identify lncRNA Malat-1 as a necessary partner for PRC2-Ezh1-dependent response to oxidative stress. We show that in this pathway, PRC2-EZH1 dynamic assembly, and in turn stress induced skeletal muscle targeted genes repression, depends specifically on Malat-1. Our study reports about PRC2-RNA interactions in the physiological context of adaptive oxidative stress response and identifies the first lncRNA involved in PRC2-Ezh1 function.
PRC2 介导的表观遗传功能涉及与长非编码 RNA（lncRNA）的相互作用。尽管在发育程序的背景下已经阐明了其中一些 RNA 的身份，但在有丝分裂后成年组织稳态中它们对应的 RNA 仍然没有被描述。为此，我们使用终末分化的有丝分裂后骨骼肌细胞，其中氧化应激通过胚胎外胚层发育（EED）穿梭到细胞核诱导 PRC2-Ezh1 的动态激活。我们确定 lncRNA Malat-1 是 PRC2-Ezh1 依赖的氧化应激反应的必要伴侣。我们表明，在这条途径中，PRC2-EZH1 的动态组装，以及随之而来的应激诱导的骨骼肌靶向基因抑制，特别依赖于 Malat-1。我们的研究报告了 PRC2-RNA 相互作用在适应性氧化应激反应的生理背景下的情况，并确定了第一个参与 PRC2-Ezh1 功能的 lncRNA。
