tRNA 2'-O-methylation modulates small RNA silencing and life span in Drosophila

Margarita T Angelova , Dilyana G Dimitrova (1) , Bruno da Silva (2) , Virginie Marchand (3) , Catherine Goyenvalle (4) , Cyrinne Achour (5) , Caroline Jacquier (6) , Valerie Bourguignon-Igel (3) , Salman Shehzada , Tina Lence , Vincent Guérineau (7) , Jean-Yves Roignant (8) , Christophe Antoniewski (9) , Laure Teysset (10) , Damien Brégeon (11) , Matthias R Schaefer , Yuri Motorin , Clément Carré

1 IBPS - Institut de Biologie Paris Seine
2 LAGEP - Laboratoire d'automatique et de génie des procédés
3 IBSLor - Ingénierie, Biologie et Santé en Lorraine
4 NPA - Neurobiologie des processus adaptatifs
5 UPD7 - Université Paris Diderot - Paris 7
6 LPNC - Laboratoire de Psychologie et NeuroCognition
7 ICSN - Institut de Chimie des Substances Naturelles
8 IMB - Institute of Molecular Biology [Mainz, Germany]
9 IBPS-Artbio - Bioinformatique [IBPS]
10 LBD - Laboratoire de Biologie du Développement
11 IGM - Institut de génétique et microbiologie [Orsay]

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 tRNA Phe , tRNA Trp and tRNA Leu , 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.

Domains: Life Sciences [q-bio]; Genomics [q-bio.GN]

Margarita T Angelova, Dilyana G Dimitrova, Bruno da Silva, Virginie Marchand, Catherine Goyenvalle, et al.. tRNA 2'-O-methylation modulates small RNA silencing and life span in Drosophila. 2019. ⟨hal-02415561⟩