TY - JOUR T1 - tRNA 2’-O-methylation modulates small RNA silencing and life span in <em>Drosophila</em> JF - bioRxiv DO - 10.1101/699934 SP - 699934 AU - Margarita T. Angelova AU - Dilyana G. Dimitrova AU - Bruno Da Silva AU - Virginie Marchand AU - Catherine Goyenvalle AU - Cyrinne Achour AU - Caroline Jacquier AU - Valérie Bourguignon-Igel AU - Salman Shehzada AU - Vincent Guerineau AU - Jean-Yves Roignant AU - Christophe Antoniewski AU - Laure Teysset AU - Damien Bregeon AU - Matthias R. Schaefer AU - Yuri Motorin AU - Clément Carré Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/11/699934.abstract N2 - 2’-O-methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two novel Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1, respectively. Genetic knockout studies together with MALDI-TOF mass spectrometry and RiboMethSeq mapping revealed that CG7009 is responsible for methylating the wobble position in tRNAPhe, tRNATrp and tRNALeu, while subsequently, CG5220 methylates position C32 in the same tRNAs and targets also additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as life span reduction, small RNA pathways dysfunction and increased sensitivity to RNA virus infections. Our results provide the first detailed characterization of two TRM7 family members in Drosophila and uncover a molecular link between enzymes catalysing Nm at specific tRNAs and small RNA-induced gene silencing pathways. ER -