title: Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate translation initiation.
abstract: Adaptation to the host cell environment to efficiently take-over the host cell's machinery is crucial in particular for small RNA viruses like picornaviruses that come with only small RNA genomes and replicate exclusively in the cytosol. Their Internal Ribosome Entry Site (IRES) elements are specific RNA structures that facilitate the 5' end-independent internal initiation of translation both under normal conditions and when the cap-dependent host protein synthesis is shut-down in infected cells. A longstanding issue is which host factors play a major role in this internal initiation. Here, we show that the functionally most important domain V of the poliovirus IRES uses tRNA(Gly) anticodon stem-loop mimicry to recruit glycyl-tRNA synthetase (GARS) to the apical part of domain V, adjacent to the binding site of the key initiation factor eIF4G. The binding of GARS promotes the accommodation of the initiation region of the IRES in the mRNA binding site of the ribosome, thereby greatly enhancing the activity of the IRES at the step of the 48S initiation complex formation. Moonlighting functions of GARS that may be additionally needed for other events of the virus-host cell interaction are discussed.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Building 40, Moscow 119991, Russian Federation.
authors.forename: Dmitri E
authors.initials: DE
authors.lastname: Andreev
authors.forename: Juliane
authors.initials: J
authors.lastname: Hirnet
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Terenin
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Dmitriev
authors.forename: Michael
authors.initials: M
authors.lastname: Niepmann
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Shatsky
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D006032:Glycine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010442:Peptide Chain Initiation, Translational; D017955:Poliovirus / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012353:RNA, Transfer, Gly / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D012353:RNA, Transfer, Gly; D012367:RNA, Viral; D006032:Glycine-tRNA Ligase