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Genes Dev. 2018 Mar 1;32(5-6):415-429. doi: 10.1101/gad.309146.117. Epub 2018 Mar 13.

Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.

Author information

1
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
2
University of Basel, Basel 4002, Switzerland.
3
Institute of Molecular Biology, 55128 Mainz, Germany.
4
School of Life Science, Faculty of Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom.
5
School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
6
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
7
Bioinformatics Core Facility, Institute of Molecular Biology, 55128 Mainz, Germany.
8
Swiss Institute of Bioinformatics, Basel 4058, Switzerland.
9
Laboratory of Cell Biology and Neurobiology, Department of Animal Biology, University of Pavia, Pavia 27100, Italy.
10
Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
#
Contributed equally

Abstract

N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila We demonstrate that Flacc promotes m6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m6A machinery.

KEYWORDS:

Flacc; RNA modifications; Zc3h13; m6A; methyltransferase complex; sex determination

PMID:
29535189
PMCID:
PMC5900714
DOI:
10.1101/gad.309146.117
[Indexed for MEDLINE]
Free PMC Article

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