title: Retroviral GAG proteins recruit AGO2 on viral RNAs without affecting RNA accumulation and translation.
abstract: Cellular micro(mi)RNAs are able to recognize viral RNAs through imperfect micro-homologies. Similar to the miRNA-mediated repression of cellular translation, this recognition is thought to tether the RNAi machinery, in particular Argonaute 2 (AGO2) on viral messengers and eventually to modulate virus replication. Here, we unveil another pathway by which AGO2 can interact with retroviral mRNAs. We show that AGO2 interacts with the retroviral Group Specific Antigen (GAG) core proteins and preferentially binds unspliced RNAs through the RNA packaging sequences without affecting RNA stability or eliciting translation repression. Using RNAi experiments, we provide evidences that these interactions, observed with both the human immunodeficiency virus 1 (HIV-1) and the primate foamy virus 1 (PFV-1), are required for retroviral replication. Taken together, our results place AGO2 at the core of the retroviral life cycle and reveal original AGO2 functions that are not related to miRNAs and translation repression.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier UMR 5535 CNRS, 1919 route de Mende, F-34293 Montpellier cedex 5, France.
authors.forename: Manuella
authors.initials: M
authors.lastname: Bouttier
authors.forename: Anne
authors.initials: A
authors.lastname: Saumet
authors.forename: Marion
authors.initials: M
authors.lastname: Peter
authors.forename: Valérie
authors.initials: V
authors.lastname: Courgnaud
authors.forename: Ute
authors.initials: U
authors.lastname: Schmidt
authors.forename: Chantal
authors.initials: C
authors.lastname: Cazevieille
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Charles-Henri
authors.initials: CH
authors.lastname: Lecellier
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D002460:Cell Line; D015683:Gene Products, gag / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics* / Q000502:physiology; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
chemical_list: D060565:Argonaute Proteins; D015683:Gene Products, gag; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral