PMID- 19106142
OWN - NLM
STAT- MEDLINE
DCOM- 20090401
LR  - 20220309
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 37
IP  - 3
DP  - 2009 Feb
TI  - Analysis of natural variants of the hepatitis C virus internal ribosome entry 
      site reveals that primary sequence plays a key role in cap-independent 
      translation.
PG  - 957-71
LID - 10.1093/nar/gkn1022 [doi]
AB  - The HCV internal ribosome entry site (IRES) spans a region of approximately 340 
      nt that encompasses most of the 5' untranslated region (5'UTR) of the viral mRNA 
      and the first 24-40 nt of the core-coding region. To investigate the implication 
      of altering the primary sequence of the 5'UTR on IRES activity, naturally 
      occurring variants of the 5'UTR were isolated from clinical samples and analyzed. 
      The impact of the identified mutations on translation was evaluated in the 
      context of RLuc/FLuc bicistronic RNAs. Results show that depending on their 
      location within the RNA structure, these naturally occurring mutations cause a 
      range of effects on IRES activity. However, mutations within subdomain IIId 
      hinder HCV IRES-mediated translation. In an attempt to explain these data, the 
      dynamic behavior of the subdomain IIId was analyzed by means of molecular 
      dynamics (MD) simulations. Despite the loss of function, MD simulations predicted 
      that mutant G266A/G268U possesses a structure similar to the wt-RNA. This 
      prediction was validated by analyzing the secondary structure of the isolated 
      IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg(2+) 
      ions. These data strongly suggest that the primary sequence of subdomain IIId 
      plays a key role in HCV IRES-mediated translation.
FAU - Barria, Maria Ines
AU  - Barria MI
AD  - Laboratorio de Virologia Molecular, Centro de Investigaciones Medicas, Facultad 
      de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile.
FAU - Gonzalez, Angel
AU  - Gonzalez A
FAU - Vera-Otarola, Jorge
AU  - Vera-Otarola J
FAU - Leon, Ursula
AU  - Leon U
FAU - Vollrath, Valeska
AU  - Vollrath V
FAU - Marsac, Delphine
AU  - Marsac D
FAU - Monasterio, Octavio
AU  - Monasterio O
FAU - Perez-Acle, Tomas
AU  - Perez-Acle T
FAU - Soza, Alejandro
AU  - Soza A
FAU - Lopez-Lastra, Marcelo
AU  - Lopez-Lastra M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081223
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA Caps)
RN  - 0 (RNA, Viral)
RN  - 0 (Regulatory Sequences, Ribonucleic Acid)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Base Sequence
MH  - Cell Line
MH  - Circular Dichroism
MH  - Hepacivirus/*genetics
MH  - Hepatitis C, Chronic/virology
MH  - Humans
MH  - Models, Molecular
MH  - Mutation
MH  - *Peptide Chain Initiation, Translational
MH  - RNA Caps/metabolism
MH  - RNA, Viral/blood/*chemistry
MH  - *Regulatory Sequences, Ribonucleic Acid
PMC - PMC2647302
EDAT- 2008/12/25 09:00
MHDA- 2009/04/02 09:00
PMCR- 2008/12/23
CRDT- 2008/12/25 09:00
PHST- 2008/12/25 09:00 [entrez]
PHST- 2008/12/25 09:00 [pubmed]
PHST- 2009/04/02 09:00 [medline]
PHST- 2008/12/23 00:00 [pmc-release]
AID - gkn1022 [pii]
AID - 10.1093/nar/gkn1022 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2009 Feb;37(3):957-71. doi: 10.1093/nar/gkn1022. Epub 2008 Dec 
      23.