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Hepatitis C virus genomic RNA dimerization is mediated via a kissing complex intermediate

Authors
 SUMANGALA SHETTY  ;  SEUNGTAEK KIM  ;  TETSURO SHIMAKAMI  ;  STANLEY M. LEMON  ;  MIHAELA-RITA MIHAILESCU 
Citation
 RNA, Vol.16(5) : 913-925, 2010 
Journal Title
RNA
ISSN
 1355-8382 
Issue Date
2010
MeSH
3' Untranslated Regions ; Base Sequence ; Conserved Sequence ; Dimerization ; Genome, Viral ; Hepacivirus/genetics* ; Hepacivirus/metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation* ; Protein Structure, Tertiary ; RNA, Viral/chemistry* ; RNA, Viral/genetics* ; Spectrometry, Fluorescence ; Viral Core Proteins/chemistry ; Viral Core Proteins/metabolism
Keywords
HCV ; core protein ; X RNA ; RNA kissing complex ; fluorescence spectroscopy ; 2-amino purine
Abstract
With over 200 million people infected with hepatitis C virus (HCV) worldwide, there is a need for more effective and better-tolerated therapeutic strategies. The HCV genome is a positive-sense; single-stranded RNA encoding a large polyprotein cleaved at multiple sites to produce at least ten proteins, among them an error-prone RNA polymerase that confers a high mutation rate. Despite considerable overall sequence diversity, in the 3'-untranslated region of the HCV genomic RNA there is a 98-nucleotide (nt) sequence named X RNA, the first 55 nt of which (X55 RNA) are 100% conserved among all HCV strains. The X55 region has been suggested to be responsible for in vitro dimerization of the genomic RNA in the presence of the viral core protein, although the mechanism by which this occurs is unknown. In this study, we analyzed the X55 region and characterized the mechanism by which it mediates HCV genomic RNA dimerization. Similar to a mechanism proposed previously for the human immunodeficiency 1 virus (HIV-1) genome, we show that dimerization of the HCV genome involves formation of a kissing complex intermediate, which is converted to a more stable extended duplex conformation in the presence of the core protein. Mutations in the dimer linkage sequence loop sequence that prevent RNA dimerization in vitro significantly reduced but did not completely ablate the ability of HCV RNA to replicate or produce infectious virus in transfected cells.
Files in This Item:
T201006202.pdf Download
DOI
10.1261/rna.1960410
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Seung Taek(김승택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158117
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