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 Kalantry; Lu Wang; Edward M. Schaeffer; Hengyao Niu; Xuesen Dong; Wei Zhao; Kaifu Chen; Qi Cao

doi:10.1038/s41556-021-00653-6

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 journal › Article › peer-review

82 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 language	English (US)
Pages (from-to)	341-354
Number of pages	14
Journal	Nature Cell Biology
Volume	23
Issue number	4
DOIs	https://doi.org/10.1038/s41556-021-00653-6
State	Published - Apr 2021

ASJC Scopus subject areas

Cell Biology

Access to Document

10.1038/s41556-021-00653-6

Cite this

Yi, Y., Li, Y., Meng, Q., Li, Q., Li, F., Lu, B., Shen, J., Fazli, L., Zhao, D., Li, C., Jiang, W., Wang, R., Liu, Q., Szczepanski, A., Li, Q., Qin, W., Weiner, A. B., Lotan, T. L., Ji, Z., ... Cao, Q. (2021). A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation. Nature Cell Biology, 23(4), 341-354. https://doi.org/10.1038/s41556-021-00653-6

Yi, Y, Li, Y, Meng, Q, Li, Q, Li, F, Lu, B, Shen, J, Fazli, L, Zhao, D, Li, C, Jiang, W, Wang, R, Liu, Q, Szczepanski, A, Li, Q, Qin, W, Weiner, AB, Lotan, TL, Ji, Z, Kalantry, S, Wang, L, Schaeffer, EM, Niu, H, Dong, X, Zhao, W, Chen, K & Cao, Q 2021, 'A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation', Nature Cell Biology, vol. 23, no. 4, pp. 341-354. https://doi.org/10.1038/s41556-021-00653-6

@article{f464b135dd2a4668a5b5b262848e62b8,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = apr,

doi = "10.1038/s41556-021-00653-6",

language = "English (US)",

volume = "23",

pages = "341--354",

journal = "Nature Cell Biology",

issn = "1465-7392",

publisher = "Nature Research",

number = "4",

}

TY - JOUR

T1 - A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation

AU - Yi, Yang

AU - Li, Yanqiang

AU - Meng, Qingshu

AU - Li, Qiaqia

AU - Li, Fuxi

AU - Lu, Bing

AU - Shen, Jiangchuan

AU - Fazli, Ladan

AU - Zhao, Dongyu

AU - Li, Chao

AU - Jiang, Weihua

AU - Wang, Rui

AU - Liu, Qipeng

AU - Szczepanski, Aileen

AU - Li, Qianru

AU - Qin, Wei

AU - Weiner, Adam B.

AU - Lotan, Tamara L.

AU - Ji, Zhe

AU - Kalantry, Sundeep

AU - Wang, Lu

AU - Schaeffer, Edward M.

AU - Niu, Hengyao

AU - Dong, Xuesen

AU - Zhao, Wei

AU - Chen, Kaifu

AU - Cao, Qi

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85103596308

UR - https://www.scopus.com/inward/citedby.url?scp=85103596308&partnerID=8YFLogxK

U2 - 10.1038/s41556-021-00653-6

DO - 10.1038/s41556-021-00653-6

M3 - Article

C2 - 33795875

AN - SCOPUS:85103596308

SN - 1465-7392

VL - 23

SP - 341

EP - 354

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 4

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this