PMID- 18567818
OWN - NLM
STAT- MEDLINE
DCOM- 20080812
LR  - 20211020
IS  - 1469-9001 (Electronic)
IS  - 1355-8382 (Print)
IS  - 1355-8382 (Linking)
VI  - 14
IP  - 8
DP  - 2008 Aug
TI  - Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus 
      internal ribosome entry site elements in their 5' untranslated regions are 
      efficiently translated in cells by a cap-dependent mechanism.
PG  - 1671-80
LID - 10.1261/rna.1039708 [doi]
AB  - The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved 
      either by a 5' cap-dependent mechanism or through internal initiation directed by 
      an internal ribosome entry site (IRES). Picornavirus IRES elements, located in 
      the 5' untranslated region (5'UTR), contain extensive secondary structure and 
      multiple upstream AUG codons. These features can be expected to inhibit 
      cap-dependent initiation of translation. However, we have now shown that certain 
      mutant hepatitis C virus-like picornavirus IRES elements (from porcine 
      teschovirus-1 and avian encephalomyelitis virus), which are unable to direct 
      internal initiation, are not significant barriers to efficient translation of 
      capped monocistronic mRNAs that contain these defective elements within their 
      5'UTRs. Moreover, the translation of these mRNAs is highly sensitive to the 
      expression of an enterovirus 2A protease (which induces cleavage of eIF4G) and is 
      also inhibited by hippuristanol, a specific inhibitor of eIF4A function, in 
      contrast to their parental wild-type IRES elements. These results provide a 
      possible basis for the evolution of viral IRES elements within the context of 
      functional mRNAs that are translated by a cap-dependent mechanism.
FAU - Belsham, Graham J
AU  - Belsham GJ
AD  - National Veterinary Institute, Technical University of Denmark, Lindholm, 
      DK-4771, Kalvehave, Denmark. grbe@vet.dtu.dk
FAU - Nielsen, Inge
AU  - Nielsen I
FAU - Normann, Preben
AU  - Normann P
FAU - Royall, Elizabeth
AU  - Royall E
FAU - Roberts, Lisa O
AU  - Roberts LO
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080620
PL  - United States
TA  - RNA
JT  - RNA (New York, N.Y.)
JID - 9509184
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (RNA Caps)
RN  - 0 (RNA, Messenger)
RN  - 0 (Regulatory Sequences, Ribonucleic Acid)
RN  - 0 (Sterols)
RN  - 0 (hippuristanol)
SB  - IM
MH  - 5' Untranslated Regions/chemistry/metabolism
MH  - Eukaryotic Initiation Factor-4G/antagonists & inhibitors
MH  - Humans
MH  - Peptide Chain Initiation, Translational
MH  - Picornaviridae/chemistry/*genetics/metabolism
MH  - Protein Biosynthesis
MH  - RNA Caps/metabolism
MH  - RNA, Messenger/chemistry/genetics
MH  - *Regulatory Sequences, Ribonucleic Acid
MH  - Ribosomes/metabolism
MH  - Sterols/pharmacology
PMC - PMC2491466
EDAT- 2008/06/24 09:00
MHDA- 2008/08/13 09:00
PMCR- 2009/02/01
CRDT- 2008/06/24 09:00
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/08/13 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
PHST- 2009/02/01 00:00 [pmc-release]
AID - rna.1039708 [pii]
AID - RA [pii]
AID - 10.1261/rna.1039708 [doi]
PST - ppublish
SO  - RNA. 2008 Aug;14(8):1671-80. doi: 10.1261/rna.1039708. Epub 2008 Jun 20.