Lence, T., Akhtar, J., Bayer, M., Schmid, K., Spindler, L., Ho, C.H., Kreim, N., Andrade-Navarro, M.A., Poeck, B., Helm, M., Roignant, J.Y. (2016). m(6)A modulates neuronal functions and sex determination in Drosophila.  Nature 540(7632): 242--247.

FBrf0234211

Research paper

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.