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Here, we showed that the Quaking protein (Qki) in microglia was greatly induced by demyelination in the brains of both mice and humans. Deletion of the Quaking gene (Qk) in microglia severely impaired the clearance of myelin debris. Transcriptomic profiling indicated that depletion of Qki impaired total RNA levels and splicing of the genes involved in phagosome formation and maturation. RNA immunoprecipitation (RIP) confirmed the physical interactions between the Qki protein and the mRNAs of Qki targets that are involved in phagocytosis, indicating that Qki regulates their RNA stability. Both Qki depletion and inhibition of Qki target Cd36 greatly reduced the phagocytic activity of microglia and macrophages. The defective uptake and degradation of myelin debris caused by Qki depletion in microglia resulted in unresolved myelin debris that impaired axon integrity, oligodendrocyte maturation, and subsequent remyelination. Thus, our results demonstrate that Qki is an essential regulator of microglia\u2019s phagocytic activity under demyelinating conditions.<\/jats:p>","DOI":"10.1084\/jem.20190348","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T18:44:08Z","timestamp":1602614648000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Qki is an essential regulator of microglial phagocytosis in demyelination"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-9859","authenticated-orcid":true,"given":"Jiangong","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0264-0047","authenticated-orcid":true,"given":"Congxin","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"},{"name":"Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9362-8272","authenticated-orcid":true,"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"},{"name":"Cancer Research Institute of Jilin University, The First Hospital of Jilin University, Changchun, Jilin, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6110-0393","authenticated-orcid":true,"given":"Joseph A.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"},{"name":"The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4367-5879","authenticated-orcid":true,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-1851","authenticated-orcid":true,"given":"Yunfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-9263","authenticated-orcid":true,"given":"Liang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"},{"name":"Graduate School of Biomedical Sciences, Tufts University, Boston, MA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-8225","authenticated-orcid":true,"given":"Takashi","family":"Shingu","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9970-8695","authenticated-orcid":true,"given":"Amy B.","family":"Heimberger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-7540","authenticated-orcid":true,"given":"Yiwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9760-2013","authenticated-orcid":true,"given":"Jian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 1"},{"name":"The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"2023072121130261400_bib1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/ajmg.b.30243","article-title":"Human QKI, a new candidate gene for schizophrenia involved in myelination","volume":"141B","author":"\u00c5berg","year":"2006","journal-title":"Am. 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