The 18S ribosomal RNA m 6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila

Autor: Pablo Mier, Christof Niehrs, Ludivine Wacheul, Minh Anh Vu, Michael U. Musheev, Marc Graille, Mihika Pradhan, Jean-Yves Roignant, Miguel A. Andrade-Navarro, Mariangela Spagnuolo, Denis L. J. Lafontaine, Jessica Leismann
Přispěvatelé: Institute of Molecular Biology (IMB), Johannes Gutenberg - Universität Mainz (JGU), RNA Molecular Biology, Center for Microscopy and Molecular Imaging, Fonds de la Recherche Nationale, Université Libre de Bruxelles, Charleroi-Gosselies, Belgium, Laboratoire de Biologie Structurale de la Cellule (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Division of Molecular Embryology - DKFZ-ZMBH Alliance, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), ANR-16-CE11-0003,m6A,La modification m6A des ANRm: biogenèse et rôle dans la stabilité des ARNm(2016)
Rok vydání: 2020
Předmět:
Zdroj: EMBO Reports
EMBO Reports, EMBO Press, 2020, pp.e49443. ⟨10.15252/embr.201949443⟩
EMBO Rep
EMBO Reports, EMBO Press, 2020, 21 (7), pp.e49443. ⟨10.15252/embr.201949443⟩
EMBO reports, 21 (7
ISSN: 1469-3178
1469-221X
DOI: 10.15252/embr.201949443
Popis: RNA modifications have recently emerged as an important layer of gene regulation. N6-methyladenosine (m6A) is the most prominent modification on eukaryotic messenger RNA and has also been found on noncoding RNA, including ribosomal and small nuclear RNA. Recently, several m6A methyltransferases were identified, uncovering the specificity of m6A deposition by structurally distinct enzymes. In order to discover additional m6A enzymes, we performed an RNAi screen to deplete annotated orthologs of human methyltransferase-like proteins (METTLs) in Drosophila cells and identified CG9666, the ortholog of human METTL5. We show that CG9666 is required for specific deposition of m6A on 18S ribosomal RNA via direct interaction with the Drosophila ortholog of human TRMT112, CG12975. Depletion of CG9666 yields a subsequent loss of the 18S rRNA m6A modification, which lies in the vicinity of the ribosome decoding center; however, this does not compromise rRNA maturation. Instead, a loss of CG9666-mediated m6A impacts fly behavior, providing an underlying molecular mechanism for the reported human phenotype in intellectual disability. Thus, our work expands the repertoire of m6A methyltransferases, demonstrates the specialization of these enzymes, and further addresses the significance of ribosomal RNA modifications in gene expression and animal behavior.
SCOPUS: ar.j
info:eu-repo/semantics/published
Databáze: OpenAIRE
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