Structural insight into cap-snatching and RNA synthesis by influenza polymerase.
Nature
; 516(7531): 361-6, 2014 Dec 18.
Article
in En
| MEDLINE
| ID: mdl-25409151
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Influenza A virus
/
Influenza B virus
/
DNA-Directed RNA Polymerases
/
RNA Caps
/
RNA, Viral
/
Models, Molecular
Language:
En
Journal:
Nature
Year:
2014
Document type:
Article