Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d
- Philip Knuckles1,2,12,
- Tina Lence3,12,
- Irmgard U. Haussmann4,5,
- Dominik Jacob6,
- Nastasja Kreim7,
- Sarah H. Carl1,8,
- Irene Masiello3,9,
- Tina Hares3,
- Rodrigo Villaseñor1,2,11,
- Daniel Hess1,
- Miguel A. Andrade-Navarro3,10,
- Marco Biggiogera9,
- Mark Helm6,
- Matthias Soller4,
- Marc Bühler1,2 and
- Jean-Yves Roignant3
- 1Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland;
- 2University of Basel, Basel 4002, Switzerland;
- 3Institute of Molecular Biology, 55128 Mainz, Germany;
- 4School of Life Science, Faculty of Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom;
- 5School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
- 6Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany;
- 7Bioinformatics Core Facility, Institute of Molecular Biology, 55128 Mainz, Germany;
- 8Swiss Institute of Bioinformatics, Basel 4058, Switzerland;
- 9Laboratory of Cell Biology and Neurobiology, Department of Animal Biology, University of Pavia, Pavia 27100, Italy;
- 10Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany
- Corresponding authors: j.roignant{at}imb-mainz.de, marc.buehler{at}fmi.ch
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↵12 These authors contributed equally to this work.
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.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.309146.117.
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Freely available online through the Genes & Development Open Access option.
- Received October 31, 2017.
- Accepted February 12, 2018.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
