RRC ID 65776
著者 Bawankar P, Lence T, Paolantoni C, Haussmann IU, Kazlauskiene M, Jacob D, Heidelberger JB, Richter FM, Nallasivan MP, Morin V, Kreim N, Beli P, Helm M, Jinek M, Soller M, Roignant JY.
タイトル Hakai is required for stabilization of core components of the m6A mRNA methylation machinery.
ジャーナル Nat Commun
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.
巻・号 12(1)
ページ 3778
公開日 2021-6-18
DOI 10.1038/s41467-021-23892-5
PII 10.1038/s41467-021-23892-5
PMID 34145251
PMC PMC8213727
MeSH 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*
IF 12.121
リソース情報
ショウジョウバエ pBFv-U6.2