m6A modulates neuronal functions and sex determination in Drosophila

Tina Lence; Junaid Akhtar; Marc Bayer; Katharina Schmid; Laura Spindler; Cheuk Hei Ho; Nastasja Kreim; Miguel A Andrade-Navarro; Burkhard Poeck; Mark Helm; Jean-Yves Roignant

doi:10.1038/nature20568

m⁶A modulates neuronal functions and sex determination in Drosophila

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

Authors

Affiliations

¹ Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
² Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
³ Institute of Zoology III (Neurobiology), Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
⁴ 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.
⁵ Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.

PMID: 27919077
DOI: 10.1038/nature20568

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