m 6 A modulates neuronal functions and sex determination in Drosophila

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Alternative Splicing
  • Animals
  • Behavior, Animal / physiology
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / physiology*
  • Female
  • Male
  • Methyltransferases / chemistry
  • Methyltransferases / metabolism
  • Nervous System / metabolism
  • Neurons / physiology*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phenotype
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA-Binding Proteins / genetics
  • Sex Determination Processes / genetics
  • Sex Determination Processes / physiology*

Substances

  • Drosophila Proteins
  • NITO protein, Drosophila
  • Nuclear Proteins
  • Protein Subunits
  • RNA-Binding Proteins
  • Sxl protein, Drosophila
  • Ythdc1 protein, Drosophila
  • N-methyladenosine
  • Methyltransferases
  • mRNA (2'-O-methyladenosine-N6-)-methyltransferase
  • Adenosine