Fiche publication
Date publication
mai 2025
Journal
PLoS pathogens
Auteurs
Membres identifiés du Cancéropôle Est :
Mr HAMMANN Philippe
,
Dr MEIGNIN Carine
Tous les auteurs :
Rousseau C, Morand T, Haas G, Lauret E, Kuhn L, Chicher J, Hammann P, Meignin C
Lien Pubmed
Résumé
RNA interference has a major role in the control of viral infection in insects. It is initialized by the sensing of double stranded RNA (dsRNA) by the RNAse III enzyme Dicer-2. Many in vitro studies have helped understand how Dicer-2 discriminates between different dsRNA substrate termini, however it is unclear whether the same mechanisms are at work in vivo, and notably during recognition of viral dsRNA. Indeed, although Dicer-2 associates with several dsRNA-binding proteins (dsRBPs) that can modify its specificity for a substrate, it remains unknown how Dicer-2 is able to recognize the protected termini of viral dsRNAs. In order to study how the ribonucleoprotein network of Dicer-2 impacts antiviral immunity, we used an IP-MS approach to identify in vivo interactants of different versions of GFP::Dicer-2 in transgenic lines. We provide a global overview of the partners of Dicer-2 in vivo, and reveal how this interactome is modulated by different factors such as viral infection and/or different point mutations inactivating the helicase or RNase III domains of GFP::Dicer-2. Our analysis uncovers several previously unknown Dicer-2 interactants associated with RNA granules, i.e., Me31B, Rump, eIF4E1, eIF4G1, Rin and Syncrip. Functional characterization of the candidates, both in cells and in vivo, reveals pro- and antiviral factors in the context of an infection by the picorna-like DCV virus. This work highlights protein complexes assembled around Dicer-2 in vivo, and provides a resource to investigate their contribution to antiviral RNAi and related pathways.
Mots clés
Animals, Ribonuclease III, metabolism, Drosophila melanogaster, virology, Drosophila Proteins, metabolism, RNA Helicases, metabolism, Animals, Genetically Modified, RNA, Viral, metabolism, RNA Interference, RNA, Double-Stranded, metabolism
Référence
PLoS Pathog. 2025 05;21(5):e1013093
