A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation

Yang Yi, Yanqiang Li, Qingshu Meng, Qiaqia Li, Fuxi Li, Bing Lu, Jiangchuan Shen, Ladan Fazli, Dongyu Zhao, Chao Li, Weihua Jiang, Rui Wang, Qipeng Liu, Aileen Szczepanski, Qianru Li, Wei Qin, Adam B. Weiner, Tamara L. Lotan, Zhe Ji, Sundeep KalantryLu Wang, Edward M. Schaeffer, Hengyao Niu, Xuesen Dong, Wei Zhao, Kaifu Chen, Qi Cao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Dysregulated translation is a common feature of cancer. Uncovering its governing factors and underlying mechanism are important for cancer therapy. Here, we report that enhancer of zeste homologue 2 (EZH2), previously known as a transcription repressor and lysine methyltransferase, can directly interact with fibrillarin (FBL) to exert its role in translational regulation. We demonstrate that EZH2 enhances rRNA 2′-O methylation via its direct interaction with FBL. Mechanistically, EZH2 strengthens the FBL–NOP56 interaction and facilitates the assembly of box C/D small nucleolar ribonucleoprotein. 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 cancer-related translational regulation.

Original languageEnglish (US)
Pages (from-to)341-354
Number of pages14
JournalNature Cell Biology
Volume23
Issue number4
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Cell Biology

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