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

Chromosomal Proteins, Non-Histone / genetics DNA Methylation / genetics Enhancer of Zeste Homolog 2 Protein / genetics Gene Expression Regulation, Neoplastic Genes, rRNA / genetics Humans Internal Ribosome Entry Sites / genetics Multiprotein Complexes / genetics Neoplasms / genetics Nuclear Proteins / genetics Protein Binding / genetics Protein Biosynthesis / genetics Ribonucleoproteins, Small Nucleolar / genetics

Journal

Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575

Informations de publication

Date de publication:
04 2021
Historique:
received: 22 02 2020
accepted: 24 02 2021
pubmed: 3 4 2021
medline: 29 6 2021
entrez: 2 4 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41556-021-00653-6 PMID: 33795875 PMC: PMC8162121
pubmed: 33795875
doi: 10.1038/s41556-021-00653-6
pii: 10.1038/s41556-021-00653-6
pmc: PMC8162121
mid: NIHMS1698128
doi:

Substances chimiques

Chromosomal Proteins, Non-Histone 0
Internal Ribosome Entry Sites 0
Multiprotein Complexes 0
NOP56 protein, human 0
Nuclear Proteins 0
Ribonucleoproteins, Small Nucleolar 0
fibrillarin 0
EZH2 protein, human EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein EC 2.1.1.43

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

341-354

Subventions

Organisme : NCI NIH HHS
ID : P50 CA180995
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA196390
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138192
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA207865
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD095463
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208257
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM124765
Pays : United States

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Auteurs

Yang Yi (Y)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-1958-7249

Yanqiang Li (Y)

Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Center for Bioinformatics and Computational Biology, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.

Qingshu Meng (Q)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0001-8093-7482

Qiaqia Li (Q)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Fuxi Li (F)

RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.

Bing Lu (B)

RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.

Jiangchuan Shen (J)

Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA.

Ladan Fazli (L)

Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Dongyu Zhao (D)

Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Center for Bioinformatics and Computational Biology, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.

Chao Li (C)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Weihua Jiang (W)

Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX, USA.

Rui Wang (R)

Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX, USA.

Qipeng Liu (Q)

Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX, USA.

Aileen Szczepanski (A)

Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Qianru Li (Q)

Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Wei Qin (W)

School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.

Adam B Weiner (AB)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-1912-042X

Tamara L Lotan (TL)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Zhe Ji (Z)

Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
ORCID: 0000-0002-1809-8099

Sundeep Kalantry (S)

Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0003-0763-8050

Lu Wang (L)

Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Edward M Schaeffer (EM)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0003-0699-1899

Hengyao Niu (H)

Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA.

Xuesen Dong (X)

Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
ORCID: 0000-0002-3115-3371

Wei Zhao (W)

RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.

Kaifu Chen (K)

Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA. kaifu.chen@childrens.harvard.edu.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA. kaifu.chen@childrens.harvard.edu.
Center for Bioinformatics and Computational Biology, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA. kaifu.chen@childrens.harvard.edu.
ORCID: 0000-0003-1009-4357

Qi Cao (Q)

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. qi.cao@northwestern.edu.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. qi.cao@northwestern.edu.
ORCID: 0000-0002-5140-3681

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Classifications MeSH

Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines chromosomiques nonhistones › A PRC2-independent function for EZH2 in...
Recherchemedicale.com › Phénomènes génétiques › Méthylation de l'ADN › A PRC2-independent function for EZH2 in...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines du groupe Polycomb › Complexe répresseur Polycomb-2 › Protéine-2 homologue de l'activateur de Zeste › A PRC2-independent function for EZH2 in...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › A PRC2-independent function for EZH2 in...
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