期刊
GENES & DEVELOPMENT
卷 32, 期 5-6, 页码 415-429出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.309146.117
关键词
Zc3h13; Flacc; m(6)A; methyltransferase complex; RNA modifications; sex determination
资金
- IMB Proteomics Core Facility - Deutsche Forschungsgemeinschaft [INST 247/766-1 FUGG]
- Deutsche Forschungsgemeinschaft (DFG) [RO 4681/5-1]
- Epitran COST action [CA16120]
- Novartis Research Foundation
- Swiss Science Foundation National Centre of Competence in Research RNA and Disease [141735]
- Biotechnology and Biological Sciences Research Council
- DFG SPP1784 grant
- BBSRC [BB/R002932/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/R002932/1] Funding Source: researchfish
N-6-methyladenosine (m(6)A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m(6)A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m(6)A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m(6)A levels and is involved in sex determination in Drosophila. We demonstrate that Flacc promotes m(6)A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m(6)A machinery.
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