Hakai is required for stabilization of core components of the m6A mRNA methylation machinery
| Autor: | Mohanakarthik Ponnadai Nallasivan, Irmgard U. Haussmann, Jan B. Heidelberger, Mark Helm, Violeta Morin, Tina Lence, Migle Kazlauskiene, Nastasja Kreim, Jean-Yves Roignant, Florian Richter, Chiara Paolantoni, Dominik Jacob, Martin Jinek, Matthias Soller, Petra Beli, Praveen Bawankar |
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| Přispěvatelé: | University of Zurich, Soller, Matthias, Roignant, Jean-Yves |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Science General Physics and Astronomy 610 Medicine & health 1600 General Chemistry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Ubiquitin 1300 General Biochemistry Genetics and Molecular Biology 10019 Department of Biochemistry Epigenetics Messenger RNA Multidisciplinary biology Methyltransferase complex Chemistry fungi General Chemistry Methylation biology.organism_classification 3100 General Physics and Astronomy Ubiquitin ligase Cell biology 030104 developmental biology Adenosine/analogs & derivatives Adenosine/metabolism Animals Cell Line Drosophila Proteins/genetics Drosophila Proteins/metabolism Drosophila melanogaster HeLa Cells Humans Methyltransferases/genetics Methyltransferases/metabolism RNA Processing Post-Transcriptional/genetics RNA Splicing/genetics RNA Messenger/genetics Ubiquitin-Protein Ligases/genetics Ubiquitin-Protein Ligases/metabolism biology.protein 570 Life sciences MRNA methylation 030217 neurology & neurosurgery |
| Zdroj: | Nature communications, vol. 12, no. 1, pp. 3778 Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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