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

Details

Serval ID
serval:BIB_C0C803938C71
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hakai is required for stabilization of core components of the m<sup>6</sup>A mRNA methylation machinery.
Journal
Nature communications
Author(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
Publication state
Published
Issued date
18/06/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
3778
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Funding(s)
Leverhulme Trust
Create date
19/06/2021 20:44
Last modification date
24/07/2021 5:34
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