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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159005 | GEO | 2020/12/10

REPOSITORIES: GEO

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

Project description: Not available

| S-EPMC8162121 | biostudies-literature

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

Project description:Overactivated ribosome biogenesis is a common feature of cancer. However, the underlying molecular mechanism remains elusive. Herein, we report enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, could interact with fibrillarin (FBL) directly in the nucleolus. While loss of EZH2 does not impact FBL-mediated histone H2AQ104 methylation (H2AQ104me) and 18S rRNA processing, EZH2 is proved to be involved in rRNA 2′-O methylation in a manner dependent of its interaction with FBL. Mechanistically, EZH2 strengthens the fibrillarin (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 alters translational efficiency and reduces internal ribosome entry site (IRES) activity of key oncogenes in prostate cancer. In summary, our findings reveal a novel non-methyltransferase role of EZH2 that mediates FBL functions, which may provide more options for the development of EZH2-targeting curative strategies in cancer.

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

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