m6A modulates neuronal functions and sex determination in Drosophila
m6A modulates neuronal functions and sex determination in Drosophila
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DOI：
10.1038/nature20568
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发表时间：
2016-12-08
期刊：
影响因子：
64.8
通讯作者：
Roignant, Jean-Yves
中科院分区：
文献类型：
--
作者：
Lence, Tina;Akhtar, Junaid;Roignant, Jean-Yves
N - 6 - 甲基腺苷RNA（m(6)A）是脊椎动物中一种常见的信使RNA修饰。尽管其在转录后基因表达调控中的功能开始被揭示，但m(6)A在复杂生物体发育过程中的确切作用仍不清楚。在此，我们对黑腹果蝇中甲基转移酶复合物的各个组分以及含YTH结构域的核阅读蛋白进行了全面的分子和生理特性研究。我们确定裂端蛋白家族成员Spenito是甲基转移酶复合物的一个新的真正亚基。我们进一步证明了该复合物在神经元功能和性别决定中的重要作用，并表明核内的YT521 - B蛋白是这些过程中主要的m(6)A效应因子。总之，我们的工作极大地拓展了我们对m(6)A生物学的认识，证明了这种修饰在整个动物体的基本过程中具有关键作用。
N-6-methyladenosine RNA (m(6)A) is a prevalent messenger RNA modification in vertebrates. Although its functions in the regulation of post-transcriptional gene expression are beginning to be unveiled, the precise roles of m(6)A during development of complex organisms remain unclear. Here we carry out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex, as well as of the YTH domain-containing nuclear reader protein in Drosophila melanogaster. We identify the member of the split ends protein family, Spenito, as a novel bona fide subunit of the methyltransferase complex. We further demonstrate important roles of this complex in neuronal functions and sex determination, and implicate the nuclear YT521-B protein as a main m(6)A effector in these processes. Altogether, our work substantially extends our knowledge of m(6)A biology, demonstrating the crucial functions of this modification in fundamental processes within the context of the whole animal.