Recruitment of the 40S ribosome subunit to the 3'-untranslated region (UTR) of a viral mRNA, via the eIF4 complex, facilitates cap-independent translation

J Biol Chem. 2015 May 1;290(18):11268-81. doi: 10.1074/jbc.M115.645002. Epub 2015 Mar 19.

Abstract

Barley yellow dwarf virus mRNA, which lacks both cap and poly(A) tail, has a translation element (3'-BTE) in its 3'-UTR essential for efficient translation initiation at the 5'-proximal AUG. This mechanism requires eukaryotic initiation factor 4G (eIF4G), subunit of heterodimer eIF4F (plant eIF4F lacks eIF4A), and 3'-BTE-5'-UTR interaction. Using fluorescence anisotropy, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) analysis, and toeprinting, we found that (i) 40S subunits bind to BTE (Kd = 350 ± 30 nm), (ii) the helicase complex eIF4F-eIF4A-eIF4B-ATP increases 40S subunit binding (Kd = 120 ± 10 nm) to the conserved stem-loop I of the 3'-BTE by exposing more unpaired bases, and (iii) long distance base pairing transfers this complex to the 5'-end of the mRNA, where translation initiates. Although 3'-5' interactions have been recognized as important in mRNA translation, barley yellow dwarf virus employs a novel mechanism utilizing the 3'-UTR as the primary site of ribosome recruitment.

Keywords: Plant Virus; Protein Synthesis; Protein-Nucleic Acid Interaction; RNA Structure; RNA Virus.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Adenosine Triphosphate / metabolism
  • Base Sequence
  • Eukaryotic Initiation Factor-4F / metabolism*
  • Luteovirus / genetics
  • Protein Biosynthesis*
  • Protein Isoforms / metabolism
  • RNA Caps
  • RNA Helicases / metabolism
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Ribosome Subunits, Small, Eukaryotic / metabolism*

Substances

  • 3' Untranslated Regions
  • Eukaryotic Initiation Factor-4F
  • Protein Isoforms
  • RNA Caps
  • RNA, Viral
  • Adenosine Triphosphate
  • RNA Helicases