GSE158663
Hakai is required for stabilizing core components of the m6A mRNA methylation machinery
N6-methyladenosine RNA (m6A) is the most abundant internal modification on mRNA which influences most steps of mRNA metabolism and is involved in several biological functions, including circadian clock, metabolism and embryonic stem cell differentiation. 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. Its depletion results in reduced m6A levels and altered m6A-dependent functions including sex determination. We show that its ubiquitination domain is required for dimerisation and interaction with other members of the m6A machinery, while its catalytic activity seems dispensable. Finally, we demonstrate that the loss of Hakai destabilizes the level of several subunits of the methyltransferase complex, resulting in impaired m6A deposition. Thus, our work adds new functional and molecular insights into the mechanism of the m6A mRNA writer complex. Overall design: S2R+ cells were treated with corresponding double stranded RNA three times during 6 days