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Nature. 2016 Dec 8;540(7632):242-247. doi: 10.1038/nature20568. Epub 2016 Nov 30.

m6A modulates neuronal functions and sex determination in Drosophila.

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Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Institute of Zoology III (Neurobiology), Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Kimmel Center for Biology and Medicine of the Skirball Institute, NYU School of Medicine, Department of Cell Biology, 540 First Avenue, New York, New York 10016, USA.
Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.


N6-methyladenosine RNA (m6A) 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 m6A 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 m6A effector in these processes. Altogether, our work substantially extends our knowledge of m6A biology, demonstrating the crucial functions of this modification in fundamental processes within the context of the whole animal.

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