A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation
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 inte...
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| Veröffentlicht in: | Nature cell biology 2021-04, Vol.23 (4), p.341-354 |
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| creator | Yi, Yang Li, Yanqiang Meng, Qingshu Li, Qiaqia Li, Fuxi Lu, Bing Shen, Jiangchuan Fazli, Ladan Zhao, Dongyu Li, Chao Jiang, Weihua Wang, Rui Liu, Qipeng Szczepanski, Aileen Li, Qianru Qin, Wei Weiner, Adam B. Lotan, Tamara L. Ji, Zhe Kalantry, Sundeep Wang, Lu Schaeffer, Edward M. Niu, Hengyao Dong, Xuesen Zhao, Wei Chen, Kaifu Cao, Qi |
| description | 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.
Yi et al. report that EZH2 exerts a PRC2-independent function in nucleoli, where it bridges FBL and NOP56 to facilitate rRNA methylation and subsequent IRES-dependent translation. |
| doi_str_mv | 10.1038/s41556-021-00653-6 |
| format | Article |
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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.
Yi et al. report that EZH2 exerts a PRC2-independent function in nucleoli, where it bridges FBL and NOP56 to facilitate rRNA methylation and subsequent IRES-dependent translation.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/s41556-021-00653-6</identifier><identifier>PMID: 33795875</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/47 ; 101/58 ; 13/1 ; 13/109 ; 13/51 ; 13/89 ; 14/19 ; 14/28 ; 14/63 ; 38/77 ; 631/337/1645/2570 ; 631/337/176 ; 631/337/386/1362 ; 631/337/574 ; Biomedical and Life Sciences ; Cancer ; Cancer Research ; Cell Biology ; Chromosomal Proteins, Non-Histone - genetics ; Development and progression ; Developmental Biology ; DNA Methylation - genetics ; Enhancer of Zeste Homolog 2 Protein - genetics ; Fibrillarin ; Gene Expression Regulation, Neoplastic ; Genes, rRNA - genetics ; Genetic aspects ; Genetic research ; Genetic translation ; Health aspects ; Homology ; Humans ; Internal ribosome entry site ; Internal Ribosome Entry Sites - genetics ; Life Sciences ; Lysine ; Methylation ; Methyltransferase ; Multiprotein Complexes - genetics ; Neoplasms - genetics ; Neoplasms - therapy ; Nuclear Proteins - genetics ; Nucleoli ; Oncogenes ; Protein Binding - genetics ; Protein Biosynthesis - genetics ; Ribonucleoproteins, Small Nucleolar - genetics ; Ribosomal RNA ; rRNA ; Stem Cells ; Structure ; Transcription ; Transferases ; Translation ; Translation initiation</subject><ispartof>Nature cell biology, 2021-04, Vol.23 (4), p.341-354</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-ccd75b56fa5070066d24b105c9784d4fbf29e25d559ddf7baf2a50a96a401f043</citedby><cites>FETCH-LOGICAL-c641t-ccd75b56fa5070066d24b105c9784d4fbf29e25d559ddf7baf2a50a96a401f043</cites><orcidid>0000-0001-8093-7482 ; 0000-0003-0763-8050 ; 0000-0002-1912-042X ; 0000-0003-0699-1899 ; 0000-0003-1009-4357 ; 0000-0002-1958-7249 ; 0000-0002-1809-8099 ; 0000-0002-3115-3371 ; 0000-0002-5140-3681</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41556-021-00653-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41556-021-00653-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33795875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yi, Yang</creatorcontrib><creatorcontrib>Li, Yanqiang</creatorcontrib><creatorcontrib>Meng, Qingshu</creatorcontrib><creatorcontrib>Li, Qiaqia</creatorcontrib><creatorcontrib>Li, Fuxi</creatorcontrib><creatorcontrib>Lu, Bing</creatorcontrib><creatorcontrib>Shen, Jiangchuan</creatorcontrib><creatorcontrib>Fazli, Ladan</creatorcontrib><creatorcontrib>Zhao, Dongyu</creatorcontrib><creatorcontrib>Li, Chao</creatorcontrib><creatorcontrib>Jiang, Weihua</creatorcontrib><creatorcontrib>Wang, Rui</creatorcontrib><creatorcontrib>Liu, Qipeng</creatorcontrib><creatorcontrib>Szczepanski, Aileen</creatorcontrib><creatorcontrib>Li, Qianru</creatorcontrib><creatorcontrib>Qin, Wei</creatorcontrib><creatorcontrib>Weiner, Adam B.</creatorcontrib><creatorcontrib>Lotan, Tamara L.</creatorcontrib><creatorcontrib>Ji, Zhe</creatorcontrib><creatorcontrib>Kalantry, Sundeep</creatorcontrib><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Schaeffer, Edward M.</creatorcontrib><creatorcontrib>Niu, Hengyao</creatorcontrib><creatorcontrib>Dong, Xuesen</creatorcontrib><creatorcontrib>Zhao, Wei</creatorcontrib><creatorcontrib>Chen, Kaifu</creatorcontrib><creatorcontrib>Cao, Qi</creatorcontrib><title>A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>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.
Yi et al. report that EZH2 exerts a PRC2-independent function in nucleoli, where it bridges FBL and NOP56 to facilitate rRNA methylation and subsequent IRES-dependent translation.</description><subject>101/47</subject><subject>101/58</subject><subject>13/1</subject><subject>13/109</subject><subject>13/51</subject><subject>13/89</subject><subject>14/19</subject><subject>14/28</subject><subject>14/63</subject><subject>38/77</subject><subject>631/337/1645/2570</subject><subject>631/337/176</subject><subject>631/337/386/1362</subject><subject>631/337/574</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Development and progression</subject><subject>Developmental Biology</subject><subject>DNA Methylation - genetics</subject><subject>Enhancer of Zeste Homolog 2 Protein - genetics</subject><subject>Fibrillarin</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, rRNA - genetics</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Genetic translation</subject><subject>Health aspects</subject><subject>Homology</subject><subject>Humans</subject><subject>Internal ribosome entry site</subject><subject>Internal Ribosome Entry Sites - genetics</subject><subject>Life Sciences</subject><subject>Lysine</subject><subject>Methylation</subject><subject>Methyltransferase</subject><subject>Multiprotein Complexes - genetics</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - therapy</subject><subject>Nuclear Proteins - genetics</subject><subject>Nucleoli</subject><subject>Oncogenes</subject><subject>Protein Binding - genetics</subject><subject>Protein Biosynthesis - genetics</subject><subject>Ribonucleoproteins, Small Nucleolar - genetics</subject><subject>Ribosomal 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Zhe</au><au>Kalantry, Sundeep</au><au>Wang, Lu</au><au>Schaeffer, Edward M.</au><au>Niu, Hengyao</au><au>Dong, Xuesen</au><au>Zhao, Wei</au><au>Chen, Kaifu</au><au>Cao, Qi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>23</volume><issue>4</issue><spage>341</spage><epage>354</epage><pages>341-354</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><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.
Yi et al. report that EZH2 exerts a PRC2-independent function in nucleoli, where it bridges FBL and NOP56 to facilitate rRNA methylation and subsequent IRES-dependent translation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33795875</pmid><doi>10.1038/s41556-021-00653-6</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-8093-7482</orcidid><orcidid>https://orcid.org/0000-0003-0763-8050</orcidid><orcidid>https://orcid.org/0000-0002-1912-042X</orcidid><orcidid>https://orcid.org/0000-0003-0699-1899</orcidid><orcidid>https://orcid.org/0000-0003-1009-4357</orcidid><orcidid>https://orcid.org/0000-0002-1958-7249</orcidid><orcidid>https://orcid.org/0000-0002-1809-8099</orcidid><orcidid>https://orcid.org/0000-0002-3115-3371</orcidid><orcidid>https://orcid.org/0000-0002-5140-3681</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2021-04, Vol.23 (4), p.341-354 |
| issn | 1465-7392 1476-4679 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8162121 |
| source | MEDLINE; Nature; SpringerLink Journals - AutoHoldings |
| subjects | 101/47 101/58 13/1 13/109 13/51 13/89 14/19 14/28 14/63 38/77 631/337/1645/2570 631/337/176 631/337/386/1362 631/337/574 Biomedical and Life Sciences Cancer Cancer Research Cell Biology Chromosomal Proteins, Non-Histone - genetics Development and progression Developmental Biology DNA Methylation - genetics Enhancer of Zeste Homolog 2 Protein - genetics Fibrillarin Gene Expression Regulation, Neoplastic Genes, rRNA - genetics Genetic aspects Genetic research Genetic translation Health aspects Homology Humans Internal ribosome entry site Internal Ribosome Entry Sites - genetics Life Sciences Lysine Methylation Methyltransferase Multiprotein Complexes - genetics Neoplasms - genetics Neoplasms - therapy Nuclear Proteins - genetics Nucleoli Oncogenes Protein Binding - genetics Protein Biosynthesis - genetics Ribonucleoproteins, Small Nucleolar - genetics Ribosomal RNA rRNA Stem Cells Structure Transcription Transferases Translation Translation initiation |
| title | A PRC2-independent function for EZH2 in regulating rRNA 2′-O methylation and IRES-dependent translation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T01%3A15%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20PRC2-independent%20function%20for%20EZH2%20in%20regulating%20rRNA%202%E2%80%B2-O%20methylation%20and%20IRES-dependent%20translation&rft.jtitle=Nature%20cell%20biology&rft.au=Yi,%20Yang&rft.date=2021-04-01&rft.volume=23&rft.issue=4&rft.spage=341&rft.epage=354&rft.pages=341-354&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/s41556-021-00653-6&rft_dat=%3Cgale_pubme%3EA657837209%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2509903316&rft_id=info:pmid/33795875&rft_galeid=A657837209&rfr_iscdi=true |