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Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.

ABSTRACT: N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m6A 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 m6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila We demonstrate that Flacc promotes m6A 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 m6A machinery.

SUBMITTER: Knuckles P 

PROVIDER: S-EPMC5900714 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m<sup>6</sup>A machinery component Wtap/Fl(2)d.

Knuckles Philip P   Lence Tina T   Haussmann Irmgard U IU   Jacob Dominik D   Kreim Nastasja N   Carl Sarah H SH   Masiello Irene I   Hares Tina T   Villaseñor Rodrigo R   Hess Daniel D   Andrade-Navarro Miguel A MA   Biggiogera Marco M   Helm Mark M   Soller Matthias M   Bühler Marc M   Roignant Jean-Yves JY  

Genes & development 20180313 5-6

<i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m<sup>6</sup>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<sup>6</sup>A methyltra  ...[more]

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