Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome.
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.
BioSciences Institute, University College Cork, Cork, Ireland.
Gary
G
Loughran
Andrew E
AE
Firth
John F
JF
Atkins
D020121:5' Untranslated Regions; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017943:Cardiovirus / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D004686:Encephalomyocarditis virus / Q000235:genetics; D018965:Frameshifting, Ribosomal; D016679:Genome, Viral; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D010802:Phylogeny; D020815:Polyproteins / Q000737:chemistry; D012367:RNA, Viral / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry*; D012689:Sequence Homology, Nucleic Acid; D017945:Theilovirus / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics*
D020121:5' Untranslated Regions; D020815:Polyproteins; D012367:RNA, Viral; D014764:Viral Proteins