A complex IRES at the 5'-UTR of a viral mRNA assembles a functional 48S complex via an uAUG intermediate

Elife. 2020 Apr 14:9:e54575. doi: 10.7554/eLife.54575.


Taking control of the cellular apparatus for protein production is a requirement for virus progression. To ensure this control, diverse strategies of cellular mimicry and/or ribosome hijacking have evolved. The initiation stage of translation is especially targeted as it involves multiple steps and the engagement of numerous initiation factors. The use of structured RNA sequences, called Internal Ribosomal Entry Sites (IRES), in viral RNAs is a widespread strategy for the exploitation of eukaryotic initiation. Using a combination of electron cryo-microscopy (cryo-EM) and reconstituted translation initiation assays with native components, we characterized how a novel IRES at the 5'-UTR of a viral RNA assembles a functional initiation complex via an uAUG intermediate. The IRES features a novel extended, multi-domain architecture, that circles the 40S head. The structures and accompanying functional data illustrate the importance of 5'-UTR regions in translation regulation and underline the relevance of the untapped diversity of viral IRESs.

Keywords: IRES; RNA; human; molecular biophysics; ribosome; structural biology; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Cryoelectron Microscopy
  • Dicistroviridae*
  • Eukaryotic Initiation Factor-3 / chemistry
  • Eukaryotic Initiation Factor-3 / metabolism
  • Eukaryotic Initiation Factor-3 / ultrastructure*
  • Humans
  • Internal Ribosome Entry Sites*
  • Models, Molecular*
  • Protein Biosynthesis / physiology
  • Protein Conformation
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • RNA, Messenger / ultrastructure
  • RNA, Viral / chemistry
  • RNA, Viral / metabolism
  • RNA, Viral / ultrastructure*
  • Ribosome Subunits / chemistry
  • Ribosome Subunits / metabolism
  • Ribosome Subunits / ultrastructure


  • 5' Untranslated Regions
  • Eukaryotic Initiation Factor-3
  • Internal Ribosome Entry Sites
  • RNA, Messenger
  • RNA, Viral

Supplementary concepts

  • Cricket paralysis virus

Associated data

  • PDB/6W2S
  • PDB/6W2T