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Curr Opin Struct Biol. 2016 Feb;36:75-84. doi: 10.1016/j.sbi.2016.01.002. Epub 2016 Jan 27.

Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases.

Author information

1
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.
2
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.

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.

PMID:
26826467
DOI:
10.1016/j.sbi.2016.01.002
[Indexed for MEDLINE]
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