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

Abstract : RNA modifications have recently emerged as an important layer of gene regulation. N6-methyladenosine (m6 A) 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 m6 A methyltransferases were identified, uncovering the specificity of m6 A deposition by structurally distinct enzymes. In order to discover additional m6 A 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 m6 A 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 m6 A modification, which lies in the vicinity of the ribosome decoding center; however, this does not compromise rRNA maturation. Instead, a loss of CG9666-mediated m6 A impacts fly behavior, providing an underlying molecular mechanism for the reported human phenotype in intellectual disability. Thus, our work expands the repertoire of m6 A methyltransferases, demonstrates the specialization of these enzymes, and further addresses the significance of ribosomal RNA modifications in gene expression and animal behavior.
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https://hal.archives-ouvertes.fr/hal-02996361
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Submitted on : Tuesday, November 10, 2020 - 2:24:08 PM
Last modification on : Thursday, July 29, 2021 - 9:34:05 AM
Long-term archiving on: : Friday, February 12, 2021 - 12:18:18 PM

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Jessica Leismann, Mariangela Spagnuolo, Mihika Pradhan, Ludivine Wacheul, Minh Anh Vu, et al.. The 18S ribosomal RNA m 6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila. EMBO Reports, EMBO Press, 2020, 21 (7), pp.e49443. ⟨10.15252/embr.201949443⟩. ⟨hal-02996361⟩

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