title: Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases.
abstract: Negative strand RNA viruses (NSVs), which may have segmented (sNSV) or non-segmented genomes (nsNSV) are responsible for numerous serious human infections such as Influenza, Measles, Rabies, Ebola, Crimean Congo Haemorrhagic Fever and Lassa Fever. Their RNA-dependent RNA polymerases transcribe and replicate the nucleoprotein coated viral genome within the context of a ribonucleoprotein particle. We review the first high resolution crystal and cryo-EM structures of representative NSV polymerases. The heterotrimeric Influenza and single-chain La Crosse orthobunyavirus polymerase structures (sNSV) show how specific recognition of both genome ends is achieved and is required for polymerase activation and how the sNSV specific 'cap-snatching' mechanism of transcription priming works. Vesicular Stomatitis Virus (nsNSV) polymerase shows a similar core architecture but has different flexibly linked C-terminal domains which perform mRNA cap synthesis. These structures pave the way for a more complete understanding of these complex, multifunctional machines which are also targets for anti-viral drug design.
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France; Unit of Virus-Host Cell Interactions (UMI 3265), University Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Reguera
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France; Unit of Virus-Host Cell Interactions (UMI 3265), University Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gerlach
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France; Unit of Virus-Host Cell Interactions (UMI 3265), University Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France. Electronic address: cusack@embl.fr.
authors.forename: Stephen
authors.initials: S
authors.lastname: Cusack
mesh_terms: D001665:Binding Sites; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000378:metabolism*; D016679:Genome, Viral; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012315:RNA Caps; D012328:RNA Viruses / Q000235:genetics* / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D012315:RNA Caps; D012367:RNA, Viral; D012321:DNA-Directed RNA Polymerases