The m(6)A pathway facilitates sex determination in Drosophila.
The m(6)A pathway facilitates sex determination in Drosophila.
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DOI：
10.1038/ncomms15737
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发表时间：
2017-07-04
影响因子：
16.6
通讯作者：
Lai EC
中科院分区：
文献类型：
--
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
保守修饰N6-甲基腺苷（m6A）调节mRNA加工和活性。在此，我们建立了果蝇系统来研究m6A通路。我们首先应用miCLIP在胚胎发生中绘制m6A，表征其m6A "写入器"复合物，验证其YTH "读取器" CG 6422和YT 521-B，并在五个m6A因子中产生突变体。虽然在剪接中具有额外作用的m6A因子是致命的，但m6A特异性突变体是可行的，但存在某些发育和行为缺陷。值得注意的是，m6A促进了主要雌性决定子Sxl，因为多个m6A组分增强了Sxl致敏背景中的雌性致死率。m6A途径直接调节Sxl加工，因为miCLIP数据揭示Sxl是主要的内含子m6A靶标，并且雌性特异性Sxl剪接在多种m6A途径突变体中受损。YT521-B是Sxl调节的显性m6 A效应子，并且YT521-B过表达可诱导雌性特异性Sxl剪接。总的来说，我们的转录组学和遗传工具包揭示了果蝇m6A通路的体内生物学功能。 N-6-甲基腺苷（m6A）是一种保守的RNA修饰，最近已成为信使RNA加工和活性的重要调节因子。在这里，作者提供的证据表明，m6A通路促进了Sxl的雌性特异性剪接，调节果蝇的性别决定。
The conserved modification N6-methyladenosine (m6A) modulates mRNA processing and activity. Here, we establish the Drosophila system to study the m6A pathway. We first apply miCLIP to map m6A across embryogenesis, characterize its m6A ‘writer’ complex, validate its YTH ‘readers’ CG6422 and YT521-B, and generate mutants in five m6A factors. While m6A factors with additional roles in splicing are lethal, m6A-specific mutants are viable but present certain developmental and behavioural defects. Notably, m6A facilitates the master female determinant Sxl, since multiple m6A components enhance female lethality in Sxl sensitized backgrounds. The m6A pathway regulates Sxl processing directly, since miCLIP data reveal Sxl as a major intronic m6A target, and female-specific Sxl splicing is compromised in multiple m6A pathway mutants. YT521-B is a dominant m6A effector for Sxl regulation, and YT521-B overexpression can induce female-specific Sxl splicing. Overall, our transcriptomic and genetic toolkit reveals in vivo biologic function for the Drosophila m6A pathway. N 6-methyladenosine (m6A) is a conserved RNA modification that has recently emerged as an important regulator of messenger RNA processing and activity. Here, the authors provide evidence that m6A pathway facilitates female-specific splicing of Sxl, regulating sex determination in Drosophila.
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影响因子：
30.3
作者：
Kennedy EM;Bogerd HP;Kornepati AV;Kang D;Ghoshal D;Marshall JB;Poling BC;Tsai K;Gokhale NS;Horner SM;Cullen BR
通讯作者：
Cullen BR
影响因子：
10.5
作者：
Ke S;Alemu EA;Mertens C;Gantman EC;Fak JJ;Mele A;Haripal B;Zucker-Scharff I;Moore MJ;Park CY;Vågbø CB;Kusśnierczyk A;Klungland A;Darnell JE Jr;Darnell RB
通讯作者：
Darnell RB
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Herold, Nadine;Will, Cindy L.;Luehrmann, Reinhard
通讯作者：
Luehrmann, Reinhard
影响因子：
2.7
作者：
Anderson, Abigail M.;Weasner, Brandon P.;Weasner, Bonnie M.;Kumar, Justin R.
通讯作者：
Kumar, Justin R.