Yi, YangLi, YanqiangMeng, QingshuLi, QiaqiaLi, FuxiLu, BingShen, JiangchuanFazli, LadanZhao, DongyuLi, ChaoJiang, WeihuaWang, RuiLiu, QipengSzczepanski, AileenLi, QianruQin, WeiWeiner, Adam B.Lotan, Tamara L.Ji, ZheKalantry, SundeepWang, LuSchaeffer, Edward M.Niu, HengyaoDong, XuesenZhao, WeiChen, KaifuCao, Qi2023-09-112021-04Yi, Yang, Yanqiang Li, Qingshu Meng, Qiaqia Li, Fuxi Li, Bing Lu, Jiangchuan Shen et al. "A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation." Nat Cell Biol 23, no. 4 (2021): 341-354. DOI: 10.1038/s41556-021-00653-61465-73921476-4679https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37377019Uncontrolled translation is a common feature of cancer. Uncovering its governing factors and underlying mechanism are important for cancer therapy. Herein, we report that enhancer of zeste homolog 2 (EZH2), previously known as a transcription repressor and lysine methyltransferase, could directly interact with fibrillarin (FBL) to exert its role in translational regulation. We demonstrate that EZH2 enhances rRNA 2′-O-Me via its direct interaction with FBL, while loss of EZH2 does not impact FBL-mediated histone H2AQ104 methylation (H2AQ104me). Mechanistically, EZH2 strengthens the FBL-NOP56 interaction by binding to both proteins and thus facilitates the assembly of box C/D small nucleolar ribonucleoprotein (box C/D snoRNP). Strikingly, EZH2 deficiency impairs the translation process globally and reduces internal ribosome entry site (IRES)-dependent translation initiation in cancer cells. Our findings reveal a previously unrecognized role of EZH2 in translational regulation, which may provide a new option for the development of EZH2-targeting curative strategies in cancer.en-USCell BiologyJournal Article2023-09-1110.1038/s41556-021-00653-6