title: m6A modulates neuronal functions and sex determination in Drosophila.
abstract: 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.
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Lence
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
authors.forename: Junaid
authors.initials: J
authors.lastname: Akhtar
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Bayer
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmid
authors.affiliation: Institute of Zoology III (Neurobiology), Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Spindler
authors.affiliation: 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.
authors.forename: Cheuk Hei
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
authors.forename: Nastasja
authors.initials: N
authors.lastname: Kreim
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany.|Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Andrade-Navarro
authors.affiliation: Institute of Zoology III (Neurobiology), Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Poeck
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Helm
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Roignant
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D005260:Female; D008297:Male; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D019849:Sex Determination Processes / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C512063:NITO protein, Drosophila; D009687:Nuclear Proteins; D021122:Protein Subunits; D016601:RNA-Binding Proteins; C067777:Sxl protein, Drosophila; C000616957:Ythdc1 protein, Drosophila; C010223:N-methyladenosine; D008780:Methyltransferases; C022556:mRNA (2'-O-methyladenosine-N6-)-methyltransferase; D000241:Adenosine