Publication Date:
2014-11-20
Description:
Influenza virus polymerase uses a capped primer, derived by 'cap-snatching' from host pre-messenger RNA, to transcribe its RNA genome into mRNA and a stuttering mechanism to generate the poly(A) tail. By contrast, genome replication is unprimed and generates exact full-length copies of the template. Here we use crystal structures of bat influenza A and human influenza B polymerases (FluA and FluB), bound to the viral RNA promoter, to give mechanistic insight into these distinct processes. In the FluA structure, a loop analogous to the priming loop of flavivirus polymerases suggests that influenza could initiate unprimed template replication by a similar mechanism. Comparing the FluA and FluB structures suggests that cap-snatching involves in situ rotation of the PB2 cap-binding domain to direct the capped primer first towards the endonuclease and then into the polymerase active site. The polymerase probably undergoes considerable conformational changes to convert the observed pre-initiation state into the active initiation and elongation states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reich, Stefan -- Guilligay, Delphine -- Pflug, Alexander -- Malet, Helene -- Berger, Imre -- Crepin, Thibaut -- Hart, Darren -- Lunardi, Thomas -- Nanao, Max -- Ruigrok, Rob W H -- Cusack, Stephen -- England -- Nature. 2014 Dec 18;516(7531):361-6. doi: 10.1038/nature14009. Epub 2014 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France [2] University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France. ; University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409151" target="_blank"〉PubMed〈/a〉
Keywords:
Catalytic Domain
;
Crystallization
;
DNA-Directed RNA Polymerases/chemistry/*metabolism
;
Gene Expression Regulation, Viral
;
Influenza A virus/chemistry/*enzymology
;
Influenza B virus/chemistry/*enzymology
;
*Models, Molecular
;
Promoter Regions, Genetic
;
Protein Binding
;
Protein Structure, Tertiary
;
*RNA Caps/chemistry/metabolism
;
RNA, Viral/*biosynthesis/*chemistry
;
Virus Replication
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
