Crossref journal-article
Cold Spring Harbor Laboratory
RNA (246)
Abstract

Hepatitis C virus (HCV) uses a structured internal ribosome entry site (IRES) RNA to recruit the translation machinery to the viral RNA and begin protein synthesis without the ribosomal scanning process required for canonical translation initiation. Different IRES structural domains are used in this process, which begins with direct binding of the 40S ribosomal subunit to the IRES RNA and involves specific manipulation of the translational machinery. We have found that upon initial 40S subunit binding, the stem–loop domain of the IRES that contains the start codon unwinds and adopts a stable configuration within the subunit's decoding groove. This configuration depends on the sequence and structure of a different stem–loop domain (domain IIb) located far from the start codon in sequence, but spatially proximal in the IRES•40S complex. Mutation of domain IIb results in misconfiguration of the HCV RNA in the decoding groove that includes changes in the placement of the AUG start codon, and a substantial decrease in the ability of the IRES to initiate translation. Our results show that two distal regions of the IRES are structurally communicating at the initial step of 40S subunit binding and suggest that this is an important step in driving protein synthesis.

Bibliography

Filbin, M. E., & Kieft, J. S. (2011). HCV IRES domain IIb affects the configuration of coding RNA in the 40S subunit’s decoding groove. RNA, 17(7), 1258–1273.

Authors 2
  1. Megan E. Filbin (first)
  2. Jeffrey S. Kieft (additional)
References 64 Referenced 61
  1. 10.1093/nar/gkn1026
  2. 10.1261/rna.2197210
  3. 10.1093/nar/23.18.3656
  4. 10.1093/nar/20.19.5041
  5. {'key': '2021112105512271000_17.7.1258.5', 'first-page': '375', 'article-title': 'A conserved RNA structure within the HCV IRES eIF3-binding site', 'volume': '9', 'year': '2002', 'journal-title': 'Nat Struct Biol'} / Nat Struct Biol / A conserved RNA structure within the HCV IRES eIF3-binding site (2002)
  6. 10.1038/nsmb1351
  7. 10.1261/rna.7214405
  8. 10.1261/rna.696508
  9. 10.1002/anie.200603807
  10. 10.1093/nar/gkp588
  11. 10.1038/nrmicro1558
  12. 10.1038/nsmb.1572
  13. 10.1016/j.bbagrm.2009.06.001 / Biochim Biophys Acta / IRES-induced conformational changes in the ribosome and the mechanism of translation initiation by internal ribosomal entry (2009)
  14. 10.1128/JVI.02403-06
  15. {'key': '2021112105512271000_17.7.1258.15', 'first-page': '955', 'article-title': 'Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA', 'volume': '2', 'year': '1996', 'journal-title': 'RNA'} / RNA / Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA (1996)
  16. 10.1128/JVI.73.2.1165-1174.1999 / J Virol / A phylogenetically conserved stem-loop structure at the 5′ border of the internal ribosome entry site of hepatitis C virus is required for cap-independent viral translation (1999)
  17. 10.1073/pnas.0407402101
  18. 10.1016/S0014-5793(01)03300-2
  19. 10.1016/j.str.2007.06.003 / Structure / A general strategy to solve the phase problem in RNA crystallography (2007)
  20. 10.1006/jmbi.1999.3095
  21. 10.1017/S1355838201001790
  22. {'key': '2021112105512271000_17.7.1258.22', 'first-page': '370', 'article-title': 'Crystal structure of an RNA tertiary domain essential to HCV IRES-mediated translation initiation', 'volume': '9', 'year': '2002', 'journal-title': 'Nat Struct Biol'} / Nat Struct Biol / Crystal structure of an RNA tertiary domain essential to HCV IRES-mediated translation initiation (2002)
  23. 10.1017/S1355838200000935
  24. 10.1128/JVI.74.14.6242-6250.2000
  25. 10.1017/S1355838200000662
  26. 10.1016/0092-8674(86)90762-2
  27. 10.1099/0022-1317-83-5-1113 / J Gen Virol / Long-range RNA-RNA interactions between distant regions of the hepatitis C virus internal ribosome entry site element (2002)
  28. 10.1093/nar/gkl155
  29. 10.1021/bi100142y
  30. 10.1016/j.jmb.2004.11.061
  31. 10.1038/sj.emboj.7601549
  32. 10.1016/j.virusres.2008.06.004
  33. 10.1038/81951
  34. 10.1038/nsb1004
  35. 10.1128/JVI.75.16.7629-7636.2001
  36. 10.1017/S1355838202029965
  37. 10.1021/ja043822v
  38. 10.1186/1741-7007-6-29
  39. 10.1074/jbc.M104128200
  40. 10.1016/j.cell.2004.09.038
  41. 10.1017/S1355838202022057
  42. 10.1016/j.molcel.2007.03.018
  43. 10.1073/pnas.0911896107
  44. 10.1006/viro.1999.9741
  45. 10.1128/MCB.16.12.6859 / Mol Cell Biol / Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry (1996)
  46. 10.1101/gad.12.1.67
  47. Pestova T , Lorsch JR , Hellen CU . 2007. The mechanism of translation initiation in eukaryotes. In Translational control in biology and medicine (ed. Mathews MB .), pp. 87–128. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
  48. 10.1038/emboj.2008.49
  49. 10.1016/j.jmb.2009.10.047
  50. 10.1128/JVI.78.9.4487-4497.2004
  51. 10.1038/emboj.2008.90
  52. 10.1126/science.1198308
  53. {'key': '2021112105512271000_17.7.1258.53', 'first-page': '867', 'article-title': 'Internal initiation of translation of hepatitis C virus RNA: The ribosome entry site is at the authentic initiation codon', 'volume': '2', 'year': '1996', 'journal-title': 'RNA'} / RNA / Internal initiation of translation of hepatitis C virus RNA: The ribosome entry site is at the authentic initiation codon (1996)
  54. 10.1128/JVI.74.2.773-783.2000
  55. 10.1126/science.1131127
  56. 10.1128/JVI.72.6.4775-4782.1998 / J Virol / Specific interaction of eukaryotic translation initiation factor 3 with the 5′ nontranslated regions of hepatitis C virus and classical swine fever virus RNAs (1998)
  57. 10.1126/science.1058409
  58. 10.1038/sj.onc.1201763
  59. 10.1038/nsmb.1445
  60. 10.1006/viro.1997.8600
  61. 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 (1993)
  62. {'key': '2021112105512271000_17.7.1258.62', 'first-page': '526', 'article-title': 'An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5′ noncoding region', 'volume': '1', 'year': '1995', 'journal-title': 'RNA'} / RNA / An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5′ noncoding region (1995)
  63. 10.1016/S0092-8674(00)00055-6
  64. 10.1016/S0092-8674(01)00435-4
Dates
Type When
Created 14 years, 2 months ago (May 24, 2011, midnight)
Deposited 3 years, 9 months ago (Nov. 21, 2021, 9:05 a.m.)
Indexed 2 months ago (June 17, 2025, 6:29 a.m.)
Issued 14 years, 2 months ago (May 23, 2011)
Published 14 years, 2 months ago (May 23, 2011)
Published Online 14 years, 2 months ago (May 23, 2011)
Published Print 14 years, 1 month ago (July 1, 2011)
Funders 0

None

@article{Filbin_2011, title={HCV IRES domain IIb affects the configuration of coding RNA in the 40S subunit’s decoding groove}, volume={17}, ISSN={1469-9001}, url={http://dx.doi.org/10.1261/rna.2594011}, DOI={10.1261/rna.2594011}, number={7}, journal={RNA}, publisher={Cold Spring Harbor Laboratory}, author={Filbin, Megan E. and Kieft, Jeffrey S.}, year={2011}, month=may, pages={1258–1273} }