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Bawankar, Praveen; Lence, Tina; Paolantoni, Chiara; Haussmann, Irmgard U.; Kazlauskiene, Migle; Jacob, Dominik; Heidelberger, Jan B.; Richter, Florian M.; Nallasivan, Mohanakarthik P.; Morin, Violeta; Kreim, Nastasja; Beli, Petra; Helm, Mark; Jinek, Martin; Soller, Matthias; Roignant, Jean-Yves

Hakai is required for stabilization of core components of the m6A mRNA methylation machinery

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  • Medientyp: E-Artikel
  • Titel: Hakai is required for stabilization of core components of the m6A mRNA methylation machinery
  • Beteiligte: Bawankar, Praveen; Lence, Tina; Paolantoni, Chiara; Haussmann, Irmgard U.; Kazlauskiene, Migle; Jacob, Dominik; Heidelberger, Jan B.; Richter, Florian M.; Nallasivan, Mohanakarthik P.; Morin, Violeta; Kreim, Nastasja; Beli, Petra; Helm, Mark; Jinek, Martin; Soller, Matthias; Roignant, Jean-Yves
  • Erschienen: Springer Science and Business Media LLC, 2021
  • Erschienen in: Nature Communications, 12 (2021) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-021-23892-5
  • ISSN: 2041-1723
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p><jats:italic>N</jats:italic><jats:sup><jats:italic>6</jats:italic></jats:sup>-methyladenosine (m<jats:sup>6</jats:sup>A) is the most abundant internal modification on mRNA which influences most steps of mRNA metabolism and is involved in several biological functions. 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>
  • Zugangsstatus: Freier Zugang