Document Detail


A small-RNA enhancer of viral polymerase activity.
MedLine Citation:
PMID:  23035211     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Influenza A virus (IAV) is an unremitting virus that results in significant morbidity and mortality worldwide. Key to the viral life cycle is the RNA-dependent RNA polymerase (RdRp), a heterotrimeric complex responsible for both transcription and replication of the segmented genome. Here, we demonstrate that the viral polymerase utilizes a small RNA enhancer to regulate enzymatic activity and maintain stoichiometric balance of the viral genome. We demonstrate that IAV synthesizes small viral RNAs (svRNAs) that interact with the viral RdRp in order to promote genome replication in a segment-specific manner. svRNAs localize to the nucleus, the site of IAV replication, are synthesized from the positive-sense genomic intermediate, and interact within a novel RNA binding channel of the polymerase PA subunit. Synthetic svRNAs promote polymerase activity in vitro, while loss of svRNA inhibits viral RNA synthesis in a segment-specific manner. Taking these observations together, we mechanistically define svRNA as a small regulatory enhancer RNA, which functions to promote genome replication and maintain segment balance through allosteric modulation of polymerase activity.
Authors:
Jasmine T Perez; Ivan Zlatev; Shilpa Aggarwal; Sailakshmi Subramanian; Ravi Sachidanandam; Baek Kim; Muthiah Manoharan; Benjamin R tenOever
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-01-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13475-85     Citation Subset:  IM    
Affiliation:
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Line
Genome, Viral
Humans
Immunoprecipitation
Influenza A virus / enzymology*,  genetics
RNA Replicase / metabolism*
Grant Support
ID/Acronym/Agency:
A1093571-01//PHS HHS; R01 AI093571/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.7.48/RNA Replicase
Comments/Corrections

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