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The amazing diversity of cap-independent translation elements in the 3'-untranslated regions of plant viral RNAs.

ABSTRACT: Many plant viral RNAs lack the 5'-cap structure that is required on all host mRNAs for interacting with essential translation initiation factors. Instead, uncapped viral RNAs take over the host translation machinery by harbouring sequences that functionally replace the 5'-cap. Recent reports reveal at least eight different classes of CITE (cap-independent translation element) located in the 3'-UTRs (untranslated regions) of various viruses. We describe how the structure and behaviour of each class of element differs from the other classes, suggesting that they recruit translation factors and, ultimately, the ribosome by diverse mechanisms. These results greatly expand our understanding of ways in which mRNAs can recruit ribosomes, and they provide insight into the regulation of virus gene expression.

SUBMITTER: Miller WA

PROVIDER: S-EPMC3081161 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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The amazing diversity of cap-independent translation elements in the 3'-untranslated regions of plant viral RNAs.

Miller W A WA Wang Z Z Treder K K

Biochemical Society transactions 20071201 Pt 6

Many plant viral RNAs lack the 5'-cap structure that is required on all host mRNAs for interacting with essential translation initiation factors. Instead, uncapped viral RNAs take over the host translation machinery by harbouring sequences that functionally replace the 5'-cap. Recent reports reveal at least eight different classes of CITE (cap-independent translation element) located in the 3'-UTRs (untranslated regions) of various viruses. We describe how the structure and behaviour of each cla ...[more]

PMID: 18031280

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Project description:Duck Tembusu virus (DTMUV) (genus Flavivirus) is a causative agent of duck egg drop syndrome and has zoonotic potential. The positive-strand RNA genomes of flaviviruses are commonly translated in a cap-dependent manner. However, dengue and Zika viruses also exhibit cap-independent translation. In this study, we show that RNAs containing 5' and 3' untranslated regions (UTRs) of DTMUV, mosquito-borne Tembusu virus (TMUV), and Japanese encephalitis virus can be translated in a cap-independent manner in mammalian, avian, and mosquito cells. The ability of the 5' UTRs of flaviviruses to direct the translation of a second open reading frame in bicistronic RNAs was much less than that observed for internal ribosome entry site (IRES) encephalomyocarditis virus, indicating a lack of substantial IRES activity. Instead, cap-independent translation of DTMUV RNA was dependent on the presence of a 3' UTR, RNA secondary structures located in both UTRs, and specific RNA sequences. Mutations inhibiting cap-independent translation decreased DTMUV proliferation in vitro and delayed, but did not prevent, the death of infected duck embryos. Thus, the 5' and 3' UTRs of DTMUV enable the virus to use a cap- and IRES-independent RNA genome translation strategy that is important for its propagation and virulence.IMPORTANCE The genus Flavivirus includes major human pathogens, as well as animal-infecting viruses with zoonotic potential. In order to counteract the threats these viruses represent, it is important to understand their basic biology to develop universal attenuation strategies. Here, we demonstrate that five different flaviviruses use cap-independent translation, indicating that the phenomenon is probably common to all members of the genus. The mechanism used for flavivirus cap-independent translation was found to be different from that of IRES-mediated translation and dependent on both 5' and 3' UTRs that act in cis As cap-independent translation was also observed in mosquito cells, its role in flavivirus infection is unlikely to be limited to the evasion of consequences of the shutoff of host translation. We found that the inhibition of cap-independent translation results in decreased viral proliferation, indicating that the strategy could be applied to produce attenuated variants of flaviviruses as potential vaccine candidates.

Dataset Information

The amazing diversity of cap-independent translation elements in the 3'-untranslated regions of plant viral RNAs.

Publications

The amazing diversity of cap-independent translation elements in the 3'-untranslated regions of plant viral RNAs.

Similar Datasets

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