PMID- 21632751
OWN - NLM
STAT- MEDLINE
DCOM- 20111004
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 16
DP  - 2011 Aug
TI  - Poly(C)-binding protein 2 interacts with sequences required for viral replication 
      in the hepatitis C virus (HCV) 5' untranslated region and directs HCV RNA 
      replication through circularizing the viral genome.
PG  - 7954-64
LID - 10.1128/JVI.00339-11 [doi]
AB  - Sequences in the 5' untranslated region (5'UTR) of hepatitis C virus (HCV) RNA is 
      important for modulating both translation and RNA replication. The translation of 
      the HCV genome depends on an internal ribosome entry site (IRES) located within 
      the 341-nucleotide 5'UTR, while RNA replication requires a smaller region. A 
      question arises whether the replication and translation functions require 
      different regions of the 5'UTR and different sets of RNA-binding proteins. Here, 
      we showed that the 5'-most 157 nucleotides of HCV RNA is the minimum 5'UTR for 
      RNA replication, and it partially overlaps with the IRES. Stem-loops 1 and 2 of 
      the 5'UTR are essential for RNA replication, whereas stem-loop 1 is not required 
      for translation. We also found that poly(C)-binding protein 2 (PCBP2) bound to 
      the replication region of the 5'UTR and associated with detergent-resistant 
      membrane fractions, which are the sites of the HCV replication complex. The 
      knockdown of PCBP2 by short hairpin RNA decreased the amounts of HCV RNA and 
      nonstructural proteins. Antibody-mediated blocking of PCBP2 reduced HCV RNA 
      replication in vitro, indicating that PCBP2 is directly involved in HCV RNA 
      replication. Furthermore, PCBP2 knockdown reduced IRES-dependent translation 
      preferentially from a dual reporter plasmid, suggesting that PCBP2 also regulated 
      IRES activity. These findings indicate that PCBP2 participates in both HCV RNA 
      replication and translation. Moreover, PCBP2 interacts with HCV 5'- and 3'UTR RNA 
      fragments to form an RNA-protein complex and induces the circularization of HCV 
      RNA, as revealed by electron microscopy. This study thus demonstrates the 
      mechanism of the participation of PCBP2 in HCV translation and replication and 
      provides physical evidence for HCV RNA circularization through 5'- and 3'UTR 
      interaction.
FAU - Wang, Linya
AU  - Wang L
AD  - Graduate Institute of Microbiology, College of Medicine, National Taiwan 
      University, Taipei 100, Taiwan.
FAU - Jeng, King-Song
AU  - Jeng KS
FAU - Lai, Michael M C
AU  - Lai MM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110601
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (PCBP2 protein, human)
RN  - 0 (RNA, Circular)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RNA, Viral)
RN  - 0 (RNA-Binding Proteins)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Antibodies, Monoclonal
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Electroporation
MH  - Genes, Reporter
MH  - Genome, Viral
MH  - Hepacivirus/*genetics/growth & development/*physiology
MH  - Humans
MH  - Inverted Repeat Sequences/genetics
MH  - Microscopy, Electron
MH  - Plasmids
MH  - Protein Biosynthesis
MH  - RNA/*metabolism
MH  - RNA Interference
MH  - RNA, Circular
MH  - RNA, Small Interfering
MH  - RNA, Viral/*biosynthesis/genetics/metabolism
MH  - RNA-Binding Proteins/genetics/immunology/*metabolism
MH  - Signal Transduction
MH  - *Virus Replication/genetics
PMC - PMC3147998
EDAT- 2011/06/03 06:00
MHDA- 2011/10/05 06:00
PMCR- 2012/02/01
CRDT- 2011/06/03 06:00
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2011/10/05 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - JVI.00339-11 [pii]
AID - 0339-11 [pii]
AID - 10.1128/JVI.00339-11 [doi]
PST - ppublish
SO  - J Virol. 2011 Aug;85(16):7954-64. doi: 10.1128/JVI.00339-11. Epub 2011 Jun 1.