Hakai is required for stabilization of core components of the m<sup>6</sup>A mRNA methylation machinery.

Détails

ID Serval
serval:BIB_C0C803938C71
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hakai is required for stabilization of core components of the m<sup>6</sup>A mRNA methylation machinery.
Périodique
Nature communications
Auteur(s)
Bawankar P., Lence T., Paolantoni C., Haussmann I.U., Kazlauskiene M., Jacob D., Heidelberger J.B., Richter F.M., Nallasivan M.P., Morin V., Kreim N., Beli P., Helm M., Jinek M., Soller M., Roignant J.Y.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
18/06/2021
Peer-reviewed
Oui
Volume
12
Numéro
1
Pages
3778
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
N <sup>6</sup> -methyladenosine (m <sup>6</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 <sup>6</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 Drosophila and human cells. In Drosophila, its depletion results in reduced m <sup>6</sup> A levels and altered m <sup>6</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 <sup>6</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 <sup>6</sup> A deposition. Our work adds functional and molecular insights into the mechanism of the m <sup>6</sup> A mRNA writer complex.
Mots-clé
Adenosine/analogs & derivatives, Adenosine/metabolism, Animals, Cell Line, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster, HeLa Cells, Humans, Methylation, Methyltransferases/genetics, Methyltransferases/metabolism, RNA Processing, Post-Transcriptional/genetics, RNA Splicing/genetics, RNA, Messenger/genetics, Ubiquitin-Protein Ligases/genetics, Ubiquitin-Protein Ligases/metabolism
Pubmed
Web of science
Open Access
Oui
Financement(s)
Leverhulme Trust
Création de la notice
19/06/2021 21:44
Dernière modification de la notice
24/07/2021 6:34
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