tRNA 2′-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila
Margarita Angelova
(1)
,
Dilyana G Dimitrova
(2, 1)
,
Bruno Da silva
(1)
,
Virginie Marchand
(3)
,
Caroline Jacquier
(2)
,
Cyrinne Achour
(2)
,
Mira Brazane
(1)
,
Catherine Goyenvalle
(2)
,
Valerie Bourguignon-Igel
(3, 4)
,
Salman Shehzada
(1)
,
Souraya Khouider
(1)
,
Tina Lence
(5)
,
Vincent Guérineau
(6)
,
Jean-Yves Roignant
(5, 7)
,
Christophe Antoniewski
(2)
,
Laure Teysset
(1)
,
Damien Bregeon
(2)
,
Yuri Motorin
(4)
,
Matthias Schaefer
(8)
,
Clément Carré
(1)
1
LBD -
Laboratoire de Biologie du Développement [IBPS]
2 IBPS - Institut de Biologie Paris Seine
3 IBSLor - Ingénierie, Biologie et Santé en Lorraine
4 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
5 IMB - Institute of Molecular Biology
6 ICSN - Institut de Chimie des Substances Naturelles
7 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode
8 Medizinische Universität Wien = Medical University of Vienna
2 IBPS - Institut de Biologie Paris Seine
3 IBSLor - Ingénierie, Biologie et Santé en Lorraine
4 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
5 IMB - Institute of Molecular Biology
6 ICSN - Institut de Chimie des Substances Naturelles
7 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode
8 Medizinische Universität Wien = Medical University of Vienna
Margarita Angelova
- Function : Author
- PersonId : 799253
- ORCID : 0000-0002-0046-9891
Dilyana G Dimitrova
- Function : Author
- PersonId : 1044755
Virginie Marchand
- Function : Author
- PersonId : 20993
- IdHAL : virginie-marchand
- ORCID : 0000-0002-8537-1139
- IdRef : 105659908
Mira Brazane
- Function : Author
- PersonId : 799560
- ORCID : 0000-0002-0638-4020
Salman Shehzada
- Function : Author
- PersonId : 799254
- ORCID : 0000-0002-4218-7622
Tina Lence
- Function : Author
- PersonId : 799255
- ORCID : 0000-0001-9377-546X
Vincent Guérineau
- Function : Author
- PersonId : 737426
- IdHAL : vincent-guerineau
- ORCID : 0000-0002-1747-5016
Jean-Yves Roignant
- Function : Author
- PersonId : 794512
- ORCID : 0000-0003-1395-2150
- IdRef : 089048261
Christophe Antoniewski
- Function : Author
- PersonId : 180858
- IdHAL : christophe-antoniewski
- ORCID : 0000-0001-7709-2116
- IdRef : 11077521X
Yuri Motorin
- Function : Author
- PersonId : 16579
- IdHAL : yuri-motorin
- ORCID : 0000-0002-8018-334X
- IdRef : 134883004
Matthias Schaefer
- Function : Author
- PersonId : 780789
- ORCID : 0000-0003-1952-8115
Clément Carré
- Function : Author
- PersonId : 756042
- ORCID : 0000-0002-9668-4288
- IdRef : 110775597
Abstract
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 Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1. 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 CG5220 methylates position C32 in the same tRNAs and also targets additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as lifespan 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 catalyzing Nm at specific tRNAs and small RNA-induced gene silencing pathways.