Nat Commun. 2021 Jun 18;12(1):3778. doi: 10.1038/s41467-021-23892-5.
Hakai is required for stabilization of core components of the m 6 A mRNA methylation machinery
Praveen Bawankar # 1, Tina Lence # 2 3, Chiara Paolantoni # 4, Irmgard U Haussmann 5 6, Migle Kazlauskiene 7, Dominik Jacob 1, Jan B Heidelberger 2, Florian M Richter 1, Mohanakarthik P Nallasivan 5, Violeta Morin 2, Nastasja Kreim 8, Petra Beli 2 9, Mark Helm 1, Martin Jinek 7, Matthias Soller 10 11, Jean-Yves Roignant 12 13Affiliations expand
Abstract
N6-methyladenosine (m6A) 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 m6A 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 Drosophila and human cells. In Drosophila, its depletion results in reduced m6A levels and altered m6A-dependent functions including sex determination. We show that its ubiquitination domain is required for dimerization and interaction with other members of the m6A 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 m6A deposition. Our work adds functional and molecular insights into the mechanism of the m6A mRNA writer complex.
- PMID: 34145251
- DOI: 10.1038/s41467-021-23892-5