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The E3 ubiquitin ligase Hakai was previously found in complex with components of the m<jats:sup>6<\/jats:sup>A methylation machinery in plants and mammalian cells but its precise function remained to be investigated. Here we show that Hakai is a conserved component of the methyltransferase complex in <jats:italic>Drosophila<\/jats:italic> and human cells. In <jats:italic>Drosophila<\/jats:italic>, its depletion results in reduced m<jats:sup>6<\/jats:sup>A levels and altered m<jats:sup>6<\/jats:sup>A-dependent functions including sex determination. We show that its ubiquitination domain is required for dimerization and interaction with other members of the m<jats:sup>6<\/jats:sup>A machinery, while its catalytic activity is dispensable. Finally, we demonstrate that the loss of Hakai destabilizes several subunits of the methyltransferase complex, resulting in impaired m<jats:sup>6<\/jats:sup>A deposition. Our work adds functional and molecular insights into the mechanism of the m<jats:sup>6<\/jats:sup>A mRNA writer complex.<\/jats:p>","DOI":"10.1038\/s41467-021-23892-5","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T10:03:33Z","timestamp":1624010613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":166,"title":["Hakai is required for stabilization of core components of the m6A mRNA methylation machinery"],"prefix":"10.1038","volume":"12","author":[{"given":"Praveen","family":"Bawankar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-546X","authenticated-orcid":false,"given":"Tina","family":"Lence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Paolantoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irmgard U.","family":"Haussmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-0410","authenticated-orcid":false,"given":"Migle","family":"Kazlauskiene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan B.","family":"Heidelberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian M.","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohanakarthik P.","family":"Nallasivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Morin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastasja","family":"Kreim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-9820","authenticated-orcid":false,"given":"Petra","family":"Beli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-0928","authenticated-orcid":false,"given":"Mark","family":"Helm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7601-210X","authenticated-orcid":false,"given":"Martin","family":"Jinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-0258","authenticated-orcid":false,"given":"Matthias","family":"Soller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-2150","authenticated-orcid":false,"given":"Jean-Yves","family":"Roignant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"23892_CR1","doi-asserted-by":"crossref","unstructured":"Roignant J. 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