Authors: Nadine Hosny El Said, Francesco Della Valle, Peng Liu, Andreu Paytuví-Gallart, Sabir Adroub, Juliette Gimenez & Valerio Orlando
- 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, Barcelona, Spain
- Epigenetics and Genome Reprogramming Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy
Date: September 2021
Publication: Nature Cell Death & Disease
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.