RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination
Maldevelopment of oligodendroglia underlies neural developmental disorders such as leukodystrophy. Precise regulation of the activity of specific transcription factors (TFs) by various posttranslational modifications (PTMs) is required to ensure proper oligodendroglial development and myelination. H...
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| description | Maldevelopment of oligodendroglia underlies neural developmental disorders such as leukodystrophy. Precise regulation of the activity of specific transcription factors (TFs) by various posttranslational modifications (PTMs) is required to ensure proper oligodendroglial development and myelination. However, the role of ubiquitination of these TFs during oligodendroglial development is yet unexplored. Here, we find that RNF220, a known leukodystrophy-related E3 ubiquitin ligase, is required for oligodendroglial development. RNF220 depletion in oligodendrocyte lineage cells impedes oligodendrocyte progenitor cell proliferation, differentiation, and (re)myelination, which consequently leads to learning and memory defects. Mechanistically, RNF220 targets Olig1/2 for K63-linked polyubiquitination and stabilization during oligodendroglial development. Furthermore, in a knock-in mouse model of leukodystrophy-related RNF220
mutation, the ubiquitination and stabilization of Olig proteins are deregulated in oligodendroglial cells. This results in pathomimetic oligodendroglial developmental defects, impaired myelination, and abnormal behaviors. Together, our evidence provides an alternative insight into PTMs of oligodendroglial TFs and how this essential process may be implicated in the etiology of leukodystrophy. |
| doi_str_mv | 10.1126/sciadv.adk3931 |
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mutation, the ubiquitination and stabilization of Olig proteins are deregulated in oligodendroglial cells. This results in pathomimetic oligodendroglial developmental defects, impaired myelination, and abnormal behaviors. Together, our evidence provides an alternative insight into PTMs of oligodendroglial TFs and how this essential process may be implicated in the etiology of leukodystrophy.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adk3931</identifier><identifier>PMID: 38324685</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; Cell Differentiation - genetics ; Demyelinating Diseases - metabolism ; Developmental Neuroscience ; Diseases and Disorders ; Mice ; Neurogenesis ; Neuroscience ; Oligodendroglia - metabolism ; SciAdv r-articles ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitination</subject><ispartof>Science advances, 2024-02, Vol.10 (6), p.eadk3931-eadk3931</ispartof><rights>Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 2024 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c236t-787bdb97b0a77878b3a18ebbeda1206dd536c4f9f133b0241c3138efe51cb8793</cites><orcidid>0000-0003-0642-7542 ; 0000-0001-8661-0659 ; 0000-0003-4698-4140 ; 0000-0002-1067-8021 ; 0000-0001-5206-1911 ; 0000-0003-1202-4635 ; 0000-0002-9965-7154 ; 0000-0002-7993-3158 ; 0000-0003-3086-3950</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849602/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849602/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38324685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yuwei</creatorcontrib><creatorcontrib>Wan, Li Pear</creatorcontrib><creatorcontrib>Song, Ning-Ning</creatorcontrib><creatorcontrib>Ding, Yu-Qiang</creatorcontrib><creatorcontrib>Zhao, Shuhua</creatorcontrib><creatorcontrib>Niu, Jianqin</creatorcontrib><creatorcontrib>Mao, Bingyu</creatorcontrib><creatorcontrib>Sheng, Nengyin</creatorcontrib><creatorcontrib>Ma, Pengcheng</creatorcontrib><title>RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Maldevelopment of oligodendroglia underlies neural developmental disorders such as leukodystrophy. Precise regulation of the activity of specific transcription factors (TFs) by various posttranslational modifications (PTMs) is required to ensure proper oligodendroglial development and myelination. However, the role of ubiquitination of these TFs during oligodendroglial development is yet unexplored. Here, we find that RNF220, a known leukodystrophy-related E3 ubiquitin ligase, is required for oligodendroglial development. RNF220 depletion in oligodendrocyte lineage cells impedes oligodendrocyte progenitor cell proliferation, differentiation, and (re)myelination, which consequently leads to learning and memory defects. Mechanistically, RNF220 targets Olig1/2 for K63-linked polyubiquitination and stabilization during oligodendroglial development. Furthermore, in a knock-in mouse model of leukodystrophy-related RNF220
mutation, the ubiquitination and stabilization of Olig proteins are deregulated in oligodendroglial cells. This results in pathomimetic oligodendroglial developmental defects, impaired myelination, and abnormal behaviors. Together, our evidence provides an alternative insight into PTMs of oligodendroglial TFs and how this essential process may be implicated in the etiology of leukodystrophy.</description><subject>Animals</subject><subject>Cell Differentiation - genetics</subject><subject>Demyelinating Diseases - metabolism</subject><subject>Developmental Neuroscience</subject><subject>Diseases and Disorders</subject><subject>Mice</subject><subject>Neurogenesis</subject><subject>Neuroscience</subject><subject>Oligodendroglia - metabolism</subject><subject>SciAdv r-articles</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitination</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1v1DAUtBCIVqVXjshHLln8kTjOCaGKFtSKSgjOlh2_LI86dmonK21_Pal2qdrTG72PmXkaQt5ztuFcqE-lR-t3G-vvZCf5K3IqZNtUoqn162f4hJyX8pcxxmulGt69JSdSS1Er3ZySh58_LoVg1Qge7QyeXitZBYx3K5xS2C8O7xecMdoZU6Rltg4DPkChtwG3dMppBoyF-iVj3NK0NpOH6HPaBrSBethBSNMIcaY2ejruIRzJ3pE3gw0Fzo_1jPy-_Prr4lt1c3v1_eLLTdULqeaq1a3zrmsds-2KtZOWa3AOvOWCKe8bqfp66AYupWOi5r3kUsMADe-dbjt5Rj4feKfFrW_2q5Vsg5kyjjbvTbJoXk4i_jHbtDOc6bpTTKwMH48MOd0vUGYzYukhBBshLcWITsiO17p5FNscVvucSskwPOlwZh5DM4fQzDG09eDDc3dP6_8jkv8ApYeYow</recordid><startdate>20240209</startdate><enddate>20240209</enddate><creator>Li, Yuwei</creator><creator>Wan, Li Pear</creator><creator>Song, Ning-Ning</creator><creator>Ding, Yu-Qiang</creator><creator>Zhao, Shuhua</creator><creator>Niu, Jianqin</creator><creator>Mao, Bingyu</creator><creator>Sheng, Nengyin</creator><creator>Ma, Pengcheng</creator><general>American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0642-7542</orcidid><orcidid>https://orcid.org/0000-0001-8661-0659</orcidid><orcidid>https://orcid.org/0000-0003-4698-4140</orcidid><orcidid>https://orcid.org/0000-0002-1067-8021</orcidid><orcidid>https://orcid.org/0000-0001-5206-1911</orcidid><orcidid>https://orcid.org/0000-0003-1202-4635</orcidid><orcidid>https://orcid.org/0000-0002-9965-7154</orcidid><orcidid>https://orcid.org/0000-0002-7993-3158</orcidid><orcidid>https://orcid.org/0000-0003-3086-3950</orcidid></search><sort><creationdate>20240209</creationdate><title>RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination</title><author>Li, Yuwei ; Wan, Li Pear ; Song, Ning-Ning ; Ding, Yu-Qiang ; Zhao, Shuhua ; Niu, Jianqin ; Mao, Bingyu ; Sheng, Nengyin ; Ma, Pengcheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c236t-787bdb97b0a77878b3a18ebbeda1206dd536c4f9f133b0241c3138efe51cb8793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Cell Differentiation - genetics</topic><topic>Demyelinating Diseases - metabolism</topic><topic>Developmental Neuroscience</topic><topic>Diseases and Disorders</topic><topic>Mice</topic><topic>Neurogenesis</topic><topic>Neuroscience</topic><topic>Oligodendroglia - metabolism</topic><topic>SciAdv r-articles</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><topic>Ubiquitination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yuwei</creatorcontrib><creatorcontrib>Wan, Li Pear</creatorcontrib><creatorcontrib>Song, Ning-Ning</creatorcontrib><creatorcontrib>Ding, Yu-Qiang</creatorcontrib><creatorcontrib>Zhao, Shuhua</creatorcontrib><creatorcontrib>Niu, Jianqin</creatorcontrib><creatorcontrib>Mao, Bingyu</creatorcontrib><creatorcontrib>Sheng, Nengyin</creatorcontrib><creatorcontrib>Ma, Pengcheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yuwei</au><au>Wan, Li Pear</au><au>Song, Ning-Ning</au><au>Ding, Yu-Qiang</au><au>Zhao, Shuhua</au><au>Niu, Jianqin</au><au>Mao, Bingyu</au><au>Sheng, Nengyin</au><au>Ma, Pengcheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2024-02-09</date><risdate>2024</risdate><volume>10</volume><issue>6</issue><spage>eadk3931</spage><epage>eadk3931</epage><pages>eadk3931-eadk3931</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Maldevelopment of oligodendroglia underlies neural developmental disorders such as leukodystrophy. Precise regulation of the activity of specific transcription factors (TFs) by various posttranslational modifications (PTMs) is required to ensure proper oligodendroglial development and myelination. However, the role of ubiquitination of these TFs during oligodendroglial development is yet unexplored. Here, we find that RNF220, a known leukodystrophy-related E3 ubiquitin ligase, is required for oligodendroglial development. RNF220 depletion in oligodendrocyte lineage cells impedes oligodendrocyte progenitor cell proliferation, differentiation, and (re)myelination, which consequently leads to learning and memory defects. Mechanistically, RNF220 targets Olig1/2 for K63-linked polyubiquitination and stabilization during oligodendroglial development. Furthermore, in a knock-in mouse model of leukodystrophy-related RNF220
mutation, the ubiquitination and stabilization of Olig proteins are deregulated in oligodendroglial cells. This results in pathomimetic oligodendroglial developmental defects, impaired myelination, and abnormal behaviors. Together, our evidence provides an alternative insight into PTMs of oligodendroglial TFs and how this essential process may be implicated in the etiology of leukodystrophy.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>38324685</pmid><doi>10.1126/sciadv.adk3931</doi><orcidid>https://orcid.org/0000-0003-0642-7542</orcidid><orcidid>https://orcid.org/0000-0001-8661-0659</orcidid><orcidid>https://orcid.org/0000-0003-4698-4140</orcidid><orcidid>https://orcid.org/0000-0002-1067-8021</orcidid><orcidid>https://orcid.org/0000-0001-5206-1911</orcidid><orcidid>https://orcid.org/0000-0003-1202-4635</orcidid><orcidid>https://orcid.org/0000-0002-9965-7154</orcidid><orcidid>https://orcid.org/0000-0002-7993-3158</orcidid><orcidid>https://orcid.org/0000-0003-3086-3950</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Differentiation - genetics Demyelinating Diseases - metabolism Developmental Neuroscience Diseases and Disorders Mice Neurogenesis Neuroscience Oligodendroglia - metabolism SciAdv r-articles Transcription Factors - genetics Transcription Factors - metabolism Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitination |
| title | RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination |
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