Alternative reading frame selection mediated by a tRNA-like domain of an internal ribosome entry site

Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):E630-9. doi: 10.1073/pnas.1111303109. Epub 2012 Jan 13.

Abstract

The dicistrovirus intergenic region internal ribosome entry site (IRES) utilizes a unique mechanism, involving P-site tRNA mimicry, to directly assemble 80S ribosomes and initiate translation at a specific non-AUG codon in the ribosomal A site. A subgroup of dicistrovirus genomes contains an additional stem-loop 5'-adjacent to the IRES and a short open reading frame (ORFx) that overlaps the viral structural polyprotein ORF (ORF2) in the +1 reading frame. Using mass spectrometry and extensive mutagenesis, we show that, besides directing ORF2 translation, the Israeli acute paralysis dicistrovirus IRES also directs ORFx translation. The latter is mediated by a UG base pair adjacent to the P-site tRNA-mimicking domain. An ORFx peptide was detected in virus-infected honey bees by multiple reaction monitoring mass spectrometry. Finally, the 5' stem-loop increases IRES activity and may couple translation of the two major ORFs of the virus. This study reveals a novel viral strategy in which a tRNA-like IRES directs precise, initiator Met-tRNA-independent translation of two overlapping ORFs.

Publication types

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

MeSH terms

  • Animals
  • Base Pairing / genetics
  • Base Sequence
  • Bees / virology
  • DNA, Complementary / genetics
  • DNA, Intergenic / genetics
  • Dicistroviridae / genetics
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-4F / metabolism
  • Molecular Sequence Data
  • Nucleic Acid Conformation*
  • Peptide Chain Initiation, Translational / genetics
  • Pupa / virology
  • RNA, Transfer / chemistry*
  • RNA, Transfer / genetics*
  • Reading Frames / genetics*
  • Ribosomes / genetics*
  • Selection, Genetic*

Substances

  • DNA, Complementary
  • DNA, Intergenic
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-4F
  • RNA, Transfer