The pathway of hepatitis C virus mRNA recruitment to the human ribosome

Christopher S. Fraser, John W B Hershey, Jennifer A. Doudna

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Eukaryotic protein synthesis begins with mRNA positioning in the ribosomal decoding channel in a process typically controlled by translation-initiation factors. Some viruses use an internal ribosome entry site (IRES) in their mRNA to harness ribosomes independently of initiation factors. We show here that a ribosome conformational change that is induced upon hepatitis C viral IRES binding is necessary but not sufficient for correct mRNA positioning. Using directed hydroxyl radical probing to monitor the assembly of IRES-containing translation-initiation complexes, we have defined a crucial step in which mRNA is stabilized upon initiator tRNA binding. Unexpectedly, however, this stabilization occurs independently of the AUG codon, underscoring the importance of initiation factor-mediated interactions that influence the configuration of the decoding channel. These results reveal how an IRES RNA supplants some, but not all, of the functions normally carried out by protein factors during initiation of protein synthesis.

Original languageEnglish (US)
Pages (from-to)397-404
Number of pages8
JournalNature Structural and Molecular Biology
Issue number4
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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