Hakai is required for stabilization of core components of the m6A mRNA methylation machinery
Bawankar, Praveen and Lence, Tina and Paolantoni, Chiara and Haussmann, Irmgard U. and Kazlauskiene, Migle and Jacob, Dominik and Heidelberger, Jan B. and Richter, Florian M. and Nallasivan, Mohanakarthik P. and Morin, Violeta and Kreim, Nastasja and Beli, Petra and Helm, Mark and Jinek, Martin and Soller, Matthias and Roignant, Jean-Yves (2021) Hakai is required for stabilization of core components of the m6A mRNA methylation machinery. Nature Communications, 12. ISSN 2041-1723
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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.
| Item Type: | Article | ||||||
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| Identification Number: | https://doi.org/10.1038/s41467-021-23892-5 | ||||||
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| Uncontrolled Keywords: | Drosophila Epigenetics Multienzyme complexes RNA modification | ||||||
| Subjects: | CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-02 - biology (non-specific) | ||||||
| Divisions: | Faculty of Health, Education and Life Sciences > School of Health Sciences | ||||||
| Depositing User: | Irmgard Haussmann | ||||||
| Date Deposited: | 02 Jul 2021 13:48 | ||||||
| Last Modified: | 12 Jan 2022 11:31 | ||||||
| URI: | https://www.open-access.bcu.ac.uk/id/eprint/11882 |
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