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PMID: 27919077 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

m6A modulates neuronal functions and sex determination in Drosophila.

Nature ·Vol. 540 ·No. 7632 ·2016-00-08 ·Pages 242-247

Lence T, Akhtar J, Bayer M, Schmid K, Spindler L, Ho CH, Kreim N, Andrade-Navarro MA, Poeck B, Helm M, Roignant JY

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.

MeSH Terms
Adenosine/analogs & derivatives,metabolism Alternative Splicing Animals Behavior, Animal/physiology Drosophila Proteins/chemistry,deficiency,genetics,metabolism Drosophila melanogaster/cytology,enzymology,physiology Female Male Methyltransferases/chemistry,metabolism Nervous System/metabolism Neurons/physiology Nuclear Proteins/chemistry,deficiency,genetics,metabolism Phenotype Protein Subunits/chemistry,metabolism RNA-Binding Proteins/genetics Sex Determination Processes/genetics,physiology
Chemicals
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
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lence Tina
Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
Akhtar Junaid
Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
Bayer Marc
Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
Schmid Katharina
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Spindler Laura
Institute of Zoology III (Neurobiology), Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Ho Cheuk Hei
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.
Kreim Nastasja
Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
Andrade-Navarro Miguel A
Institute of Molecular Biology (IMB), 55128 Mainz, Germany. | Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Poeck Burkhard
Institute of Zoology III (Neurobiology), Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Helm Mark
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Roignant Jean-Yves
Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature20568
Published
2016-00-08
Epub
2016-00-30
Pages
242-247
Language
English
Region
England
NLM ID
0410462
Subset
IM
Corrections
CommentIn
PMID: 28029164
CommentIn
PMID: 28053349
External Links
PubMed source DOI: 10.1038/nature20568 View journal details
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