Beyond RNAi: How the Dicer protein modulates the antiviral innate immune response in mammalian cells: Mammalian Dicer could regulate the innate immune response in an RNAi-independent manner as a result of losing long dsRNA processive activity.

Fiche publication

Date publication

septembre 2024

Journal

BioEssays : news and reviews in molecular, cellular and developmental biology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr PFEFFER Sébastien

Tous les auteurs :
Gaucherand L, Baldaccini M, Pfeffer S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39248656

Résumé

While Dicer plays an important antiviral role through the RNAi pathway in plants and invertebrates, its contribution to antiviral immunity in vertebrates and more specifically mammals is more controversial. The apparent limited RNAi activity in mammalian cells has been attributed to the reduced long dsRNA processive activity of mammalian Dicer, as well as a functional incompatibility between the RNAi and IFN pathways. Why Dicer has lost this antiviral activity in the profit of the IFN pathway is still unclear. We propose that the primary direct antiviral activity of Dicer has been functionally replaced by other sensors in the IFN pathway, leading to its specialization toward microRNA maturation. As a result, Dicer can regulate the innate immune response and prevent basal activation of the IFN pathway in mammals. Here, we discuss this hypothesis, highlighting how the adaptation of the helicase domain of mammalian Dicer may be key to this process.