DOI: 10.1261/rna.2342306. Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site

Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site

10.1261/rna.2342306

Crossref journal-article

Cold Spring Harbor Laboratory

RNA (246)

Abstract

The hepatitis C viral mRNA initiates translation using an internal ribosome entry site (IRES) located in the 5′ noncoding region of the viral genome. At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF3 and the ternary eIF2/GTP/Met-tRNAiMet complex, and joins 60S subunits to assemble translation-competent 80S ribosomes. Here we show that in the presence of 5 mM MgCl2, the HCV IRES can initiate translation by an alternative mechanism that does not require known initiation factors. Specifically, the HCV IRES was shown to initiate translation in a reconstituted system consisting only of purified 40S and 60S subunits, elongation factors, and aminoacylated tRNAs at high magnesium concentration. Analyses of assembled complexes supported a mechanism by which preformed 80S ribosomes can assemble directly on the HCV IRES at high cation concentrations. This mechanism is reminiscent of that employed by the divergent IRES elements in the Dicistroviridae, exemplified by the cricket paralysis virus, which mediates initiation of protein synthesis without initiator tRNA.

Bibliography

Lancaster, A. M., Jan, E., & Sarnow, P. (2006). Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site. RNA, 12(5), 894â902.

Authors 3

Alissa M. Lancaster (first)
Eric Jan (additional)
Peter Sarnow (additional)

References 44 Referenced 86

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Hershey J.W.B. Merrick W.C. (2000) in Translational control of gene expression, The pathway and mechanism of initiation of protein synthesis, ed Sonenberg N. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York), pp 33–88.
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10.1002/j.1460-2075.1994.tb06431.x / EMBO J. / Translation of encephalomyocarditis virus RNA: Parameters influencing the selection of the internal initiation site by Kaminski (1994)
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Pestova T.V. Hellen C.U. 2003. Translation elongation after assembly of ribosomes on the Cricket paralysis virus internal ribosomal entry site without initiation factors or initiator tRNA. Genes & Dev. 17:181–186. (10.1101/gad.1040803)
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10.1128/jvi.67.6.3338-3344.1993 / J. Virol. / Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism by Wang (1993)
10.1055/s-2000-9506
10.1016/S0092-8674(00)00055-6
10.1128/MCB.20.14.4990-4999.2000

Dates

Type	When
Created	19 years, 5 months ago (March 23, 2006, 9:08 p.m.)
Deposited	3 years, 9 months ago (Nov. 21, 2021, 8:46 a.m.)
Indexed	6 days, 19 hours ago (Aug. 20, 2025, 8:39 a.m.)
Issued	19 years, 5 months ago (March 23, 2006)
Published	19 years, 5 months ago (March 23, 2006)
Published Online	19 years, 5 months ago (March 23, 2006)
Published Print	19 years, 3 months ago (May 1, 2006)

Funders 0

None

BibTeX

@article{Lancaster_2006, title={Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site}, volume={12}, ISSN={1469-9001}, url={http://dx.doi.org/10.1261/rna.2342306}, DOI={10.1261/rna.2342306}, number={5}, journal={RNA}, publisher={Cold Spring Harbor Laboratory}, author={Lancaster, Alissa M. and Jan, Eric and Sarnow, Peter}, year={2006}, month=mar, pages={894–902} }

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