A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation
Nature cell biology, 2021•nature.com
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 …
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 …
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.
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