title: Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation.
abstract: The protein kinase TOR (target-of-rapamycin) upregulates translation initiation in eukaryotes, but initiation restart after long ORF translation is restricted by largely unknown pathways. The plant viral reinitiation factor transactivator-viroplasmin (TAV) exceptionally promotes reinitiation through a mechanism involving retention on 80S and reuse of eIF3 and the host factor reinitiation-supporting protein (RISP) to regenerate reinitiation-competent ribosomal complexes. Here, we show that TAV function in reinitiation depends on physical association with TOR, with TAV-TOR binding being critical for both translation reinitiation and viral fitness. Consistently, TOR-deficient plants are resistant to viral infection. TAV triggers TOR hyperactivation and S6K1 phosphorylation in planta. When activated, TOR binds polyribosomes concomitantly with polysomal accumulation of eIF3 and RISP--a novel and specific target of TOR/S6K1--in a TAV-dependent manner, with RISP being phosphorylated. TAV mutants defective in TOR binding fail to recruit TOR, thereby abolishing RISP phosphorylation in polysomes and reinitiation. Thus, activation of reinitiation after long ORF translation is more complex than previously appreciated, with TOR/S6K1 upregulation being the key event in the formation of reinitiation-competent ribosomal complexes.
authors.affiliation: Institut de Biologie Moléculaire des Plantes du CNRS, Université de Strasbourg, Strasbourg Cedex, France.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Schepetilnikov
authors.forename: Kappei
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Angèle
authors.initials: A
authors.lastname: Geldreich
authors.forename: Carole
authors.initials: C
authors.lastname: Caranta
authors.forename: Christophe
authors.initials: C
authors.lastname: Robaglia
authors.forename: Mario
authors.initials: M
authors.lastname: Keller
authors.forename: Lyubov A
authors.initials: LA
authors.lastname: Ryabova
mesh_terms: D017360:Arabidopsis; D029681:Arabidopsis Proteins; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D054884:Host-Pathogen Interactions; D047468:Immunoprecipitation; D019869:Phosphatidylinositol 3-Kinases; D011485:Protein Binding; D014176:Protein Biosynthesis; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D039621:Eukaryotic Initiation Factor-3; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D014764:Viral Proteins; C065790:viroplasmin protein, Cauliflower mosaic virus; C512171:TOR protein, Arabidopsis