Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m(6)A machinery component Wtap/Fl(2)d.
Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m(6)A machinery component Wtap/Fl(2)d.
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DOI：
10.1101/gad.309146.117
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发表时间：
2018-03-01
影响因子：
10.5
通讯作者：
Roignant JY
中科院分区：
文献类型：
--
作者：
Knuckles P;Lence T;Haussmann IU;Jacob D;Kreim N;Carl SH;Masiello I;Hares T;Villaseñor R;Hess D;Andrade-Navarro MA;Biggiogera M;Helm M;Soller M;Bühler M;Roignant JY
在这项研究中，Knuckles等人发现Flacc/Zc3h13是果蝇和小鼠中m6A甲基转移酶复合物组分的一种新的相互作用因子。他们发现Flacc通过将Fl(2)d连接到mRNA结合因子Nito来促进甲基转移酶对mRNA的募集，这为m6A机制的保护和调控提供了新的见解。n6 -甲基腺苷（m6A）是真核生物中最丰富的mRNA修饰，在多种生物过程中发挥着重要作用。m6A是由甲基转移酶样3 （Mettl3）的活性催化的，而甲基转移酶样3依赖于其他蛋白质，而这些蛋白质的确切功能尚不清楚。本研究发现Zc3h13（锌指CCCH结构域蛋白13）/Flacc [Fl(2)d相关复合物组分]是果蝇和小鼠中m6A甲基转移酶复合物组分的一个新的相互作用因子。与该复合体的其他成分一样，Flacc控制着m6A水平，并参与果蝇的性别决定。我们证明Flacc通过将Fl(2)d桥接到mrna结合因子Nito来促进m6A的沉积。总之，我们的工作促进了对m6A机制的保护和调控的分子理解。
In this study, Knuckles et al. identified Flacc/Zc3h13 as a novel interactor of m6A methyltransferase complex components in Drosophila and mice. They show that Flacc promotes the recruitment of the methyltransferase to mRNA by bridging Fl(2)d to the mRNA-binding factor Nito, providing novel insights into the conservation and regulation of the m6A machinery. 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.
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影响因子：
16.6
作者：
Kan L;Grozhik AV;Vedanayagam J;Patil DP;Pang N;Lim KS;Huang YC;Joseph B;Lin CJ;Despic V;Guo J;Yan D;Kondo S;Deng WM;Dedon PC;Jaffrey SR;Lai EC
通讯作者：
Lai EC
影响因子：
64.8
作者：
Lence, Tina;Akhtar, Junaid;Roignant, Jean-Yves
通讯作者：
Roignant, Jean-Yves
影响因子：
14.9
作者：
Kellner S;Ochel A;Thüring K;Spenkuch F;Neumann J;Sharma S;Entian KD;Schneider D;Helm M
通讯作者：
Helm M
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
50.3
作者：
Li Z;Weng H;Su R;Weng X;Zuo Z;Li C;Huang H;Nachtergaele S;Dong L;Hu C;Qin X;Tang L;Wang Y;Hong GM;Huang H;Wang X;Chen P;Gurbuxani S;Arnovitz S;Li Y;Li S;Strong J;Neilly MB;Larson RA;Jiang X;Zhang P;Jin J;He C;Chen J
通讯作者：
Chen J