The 18S ribosomal RNA m 6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila - École polytechnique Accéder directement au contenu
Article Dans Une Revue EMBO Reports Année : 2020

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

Jessica Leismann
  • Fonction : Auteur
Mariangela Spagnuolo
  • Fonction : Auteur
Mihika Pradhan
  • Fonction : Auteur
Ludivine Wacheul
Minh Anh Vu
  • Fonction : Auteur
Michael Musheev
  • Fonction : Auteur
Pablo Mier
  • Fonction : Auteur
Miguel Andrade‐navarro
  • Fonction : Auteur
Christof Niehrs
  • Fonction : Auteur
Denis Lj Lafontaine
  • Fonction : Auteur
Jean‐yves Roignant
  • Fonction : Auteur

Résumé

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.
Fichier principal
Vignette du fichier
Manuscript_Mettl5.pdf (934.87 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02996361 , version 1 (10-11-2020)

Identifiants

Citer

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, 2020, 21 (7), pp.e49443. ⟨10.15252/embr.201949443⟩. ⟨hal-02996361⟩
99 Consultations
108 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More