Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor

Christian M.T. Spahn, Eric Jan, Anke Mulder, Robert A. Grassucci, Peter Sarnow, Joachim Frank

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-like IRES elements seem to act as RNA-based translation factors.

Original languageEnglish (US)
Pages (from-to)465-475
Number of pages11
JournalCell
Volume118
Issue number4
DOIs
StatePublished - Aug 20 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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