Structures of two RNA domains essential for hepatitis C virus internal ribosome entry site function

Abstract

Translation of the hepatitis C virus (HCV) polyprotein is initiated at an internal ribosome entry site (IRES) element in the 5′ untranslated region of HCV RNA. The HCV IRES element interacts directly with the 40S subunit, and biochemical experiments have implicated RNA elements near the AUG start codon as required for IRES–40S subunit complex formation. The data we present here show that two RNA stem loops, domains IIId and IIIe, are involved in IRES–40S subunit interaction. The structures of the two RNA domains were solved by NMR spectroscopy and reveal structural features that may explain their role in IRES function.

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Figure 1
Figure 2: Structure of HCV domain IIIe stem loop.
Figure 3: Structure of HCV domain IIId stem loop.

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Acknowledgements

The authors thank E. Lau for preparation of labeled nucleotides. Supported by grants from the NIH, the Hutchinson Foundation and Eli Lilly, Inc., and a postdoctoral grant to P. J. L. from the Max Kade Foundation. The Stanford Magnetic Resonance Laboratory is supported by the Stanford University School of Medicine.

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Correspondence to Joseph D. Puglisi.

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Lukavsky, P., Otto, G., Lancaster, A. et al. Structures of two RNA domains essential for hepatitis C virus internal ribosome entry site function. Nat Struct Mol Biol 7, 1105–1110 (2000) doi:10.1038/81951

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