Journal article
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
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 59 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.
Language: | English |
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Publisher: | Cold Spring Harbor Laboratory Press |
Year: | 2008 |
Pages: | 1671-1680 |
ISSN: | 14699001 and 13558382 |
Types: | Journal article |
DOI: | 10.1261/rna.1039708 |
ORCIDs: | Belsham, Graham |
IRES SDG 3 - Good Health and Well-being hippuristanol picornavirus protein synthesis translation
5' Untranslated Regions 5' Untranslated Regions/chemistry Eukaryotic Initiation Factor-4G Eukaryotic Initiation Factor-4G/antagonists & inhibitors Humans Peptide Chain Initiation, Translational Picornaviridae Picornaviridae/chemistry Protein Biosynthesis RNA Caps RNA Caps/metabolism RNA, Messenger RNA, Messenger/chemistry Regulatory Sequences, Ribonucleic Acid Ribosomes Ribosomes/metabolism Sterols Sterols/pharmacology