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 Knuckles; Tina Lence; Irmgard Haussmann; Dominik Jacob; Nastasja Kreim; Sarah H. Carl; Irene Masiello; Tina Hares; Rodrigo Villaseñor; Daniel Hess; Miguel A. Andrade-Navarro; Marco Biggiogera; Mark Helm; Matthias Soller; Marc Bühler; Jean-Yves Roignant

doi:10.1101/gad.309146.117

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 Knuckles, Tina Lence, Irmgard Haussmann, Dominik Jacob, Nastasja Kreim, Sarah H. Carl, Irene Masiello, Tina Hares, Rodrigo Villaseñor, Daniel Hess, Miguel A. Andrade-Navarro, Marco Biggiogera, Mark Helm, Matthias Soller, Marc Bühler, Jean-Yves Roignant

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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 Mettl3, which depends on additional proteins whose precise functions remain poorly understood. Here we identified Flacc/Zc3h13 as a novel interactor of m6A methyltransferase complex components in Drosophila and mouse. 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 our molecular understanding of conservation and regulation of the m6A machinery.

Original language	English
Pages (from-to)	415-429
Number of pages	15
Journal	Genes & Development
Volume	32
Early online date	13 Mar 2018
DOIs	https://doi.org/10.1101/gad.309146.117
Publication status	Published - 2018

Bibliographical note

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/.

Keywords

Zc3h13
Flacc
m6A
methyltransferase complex
RNA modifications
sex determination

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10.1101/gad.309146.117Licence: CC BY

PublishedFinal published version, 8.86 MBLicence: CC BY

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Knuckles, P., Lence, T., Haussmann, I., Jacob, D., Kreim, N., Carl, S. H., Masiello, I., Hares, T., Villaseñor, R., Hess, D., Andrade-Navarro, M. A., Biggiogera, M., Helm, M., Soller, M., Bühler, M., & Roignant, J.-Y. (2018). Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d. Genes & Development, 32, 415-429. https://doi.org/10.1101/gad.309146.117

Knuckles, P, Lence, T, Haussmann, I, Jacob, D, Kreim, N, Carl, SH, Masiello, I, Hares, T, Villaseñor, R, Hess, D, Andrade-Navarro, MA, Biggiogera, M, Helm, M, Soller, M, Bühler, M & Roignant, J-Y 2018, 'Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d', Genes & Development, vol. 32, pp. 415-429. https://doi.org/10.1101/gad.309146.117

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

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 Mettl3, which depends on additional proteins whose precise functions remain poorly understood. Here we identified Flacc/Zc3h13 as a novel interactor of m6A methyltransferase complex components in Drosophila and mouse. 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 our molecular understanding of conservation and regulation of the m6A machinery.",

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note = "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/.",

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AU - Haussmann, Irmgard

AU - Jacob, Dominik

AU - Kreim, Nastasja

AU - Carl, Sarah H.

AU - Masiello, Irene

AU - Hares, Tina

AU - Villaseñor, Rodrigo

AU - Hess, Daniel

AU - Andrade-Navarro, Miguel A.

AU - Biggiogera, Marco

AU - Helm, Mark

AU - Soller, Matthias

AU - Bühler, Marc

AU - Roignant, Jean-Yves

N1 - 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/.

PY - 2018

Y1 - 2018

N2 - 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 Mettl3, which depends on additional proteins whose precise functions remain poorly understood. Here we identified Flacc/Zc3h13 as a novel interactor of m6A methyltransferase complex components in Drosophila and mouse. 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 our molecular understanding of conservation and regulation of the m6A machinery.

AB - 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 Mettl3, which depends on additional proteins whose precise functions remain poorly understood. Here we identified Flacc/Zc3h13 as a novel interactor of m6A methyltransferase complex components in Drosophila and mouse. 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 our molecular understanding of conservation and regulation of the m6A machinery.

KW - Zc3h13

KW - Flacc

KW - m6A

KW - methyltransferase complex

KW - RNA modifications

KW - sex determination

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DO - 10.1101/gad.309146.117

M3 - Article

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VL - 32

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JO - Genes & Development

JF - Genes & Development

ER -

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

Abstract

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Keywords

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