Hepatitis C virus IRES RNA-induced changes in the conformation of the 40s ribosomal subunit

Science. 2001 Mar 9;291(5510):1959-62. doi: 10.1126/science.1058409.


Initiation of protein synthesis in eukaryotes requires recruitment of the 40S ribosomal subunit to the messenger RNA (mRNA). In most cases, this depends on recognition of a modified nucleotide cap on the 5' end of the mRNA. However, an alternate pathway uses a structured RNA element in the 5' untranslated region of the messenger or viral RNA called an internal ribosomal entry site (IRES). Here, we present a cryo-electron microscopy map of the hepatitis C virus (HCV) IRES bound to the 40S ribosomal subunit at about 20 A resolution. IRES binding induces a pronounced conformational change in the 40S subunit and closes the mRNA binding cleft, suggesting a mechanism for IRES-mediated positioning of mRNA in the ribosomal decoding center.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions / chemistry
  • 5' Untranslated Regions / metabolism*
  • Animals
  • Base Sequence
  • Cryoelectron Microscopy
  • Hepacivirus / genetics
  • Hepacivirus / metabolism*
  • Hepacivirus / ultrastructure
  • Image Processing, Computer-Assisted
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA, Messenger / metabolism
  • RNA, Ribosomal, 18S / chemistry
  • RNA, Ribosomal, 18S / metabolism
  • RNA, Viral / chemistry
  • RNA, Viral / metabolism*
  • Rabbits
  • Ribosomes / chemistry*
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure


  • 5' Untranslated Regions
  • Macromolecular Substances
  • RNA, Messenger
  • RNA, Ribosomal, 18S
  • RNA, Viral