Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome

Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1111-9. doi: 10.1073/pnas.1102932108. Epub 2011 Oct 24.

Abstract

The genus Cardiovirus (family Picornaviridae) currently comprises the species Encephalomyocarditis virus (EMCV) and Theilovirus. Cardioviruses have a positive-sense, single-stranded RNA genome that encodes a large polyprotein (L-1ABCD-2ABC-3ABCD) that is cleaved to produce approximately 12 mature proteins. We report on a conserved ORF that overlaps the 2B-encoding sequence of EMCV in the +2 reading frame. The ORF is translated as a 128-129 amino acid transframe fusion (2B*) with the N-terminal 11-12 amino acids of 2B, via ribosomal frameshifting at a conserved GGUUUUY motif. Mutations that knock out expression of 2B* result in a small-plaque phenotype. Curiously, although theilovirus sequences lack a long ORF in the +2 frame at this genomic location, they maintain a conserved GGUUUUU motif just downstream of the 2A-2B junction, and a highly localized peak in conservation at polyprotein-frame synonymous sites suggests that theiloviruses also utilize frameshifting here, albeit into a very short +2-frame ORF. Unlike previous cases of programmed -1 frameshifting, here frameshifting is modulated by virus infection, thus suggesting a novel regulatory role for frameshifting in these viruses.

Publication types

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

MeSH terms

  • 5' Untranslated Regions
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cardiovirus / genetics*
  • Cricetinae
  • Cricetulus
  • Encephalomyocarditis virus / genetics
  • Frameshifting, Ribosomal*
  • Genome, Viral
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Open Reading Frames
  • Phylogeny
  • Polyproteins / chemistry
  • RNA, Viral / metabolism
  • Ribosomes / chemistry*
  • Sequence Homology, Nucleic Acid
  • Theilovirus / genetics
  • Viral Proteins / genetics*

Substances

  • 5' Untranslated Regions
  • Polyproteins
  • RNA, Viral
  • Viral Proteins