title: Transcriptional slippage in the positive-sense RNA virus family Potyviridae.
abstract: The family Potyviridae encompasses ~30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional "A" inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ~2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.
authors.affiliation: Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK Department of Plant Sciences, University of Cambridge, Cambridge, UK.
authors.forename: Allan
authors.initials: A
authors.lastname: Olspert
authors.affiliation: Department of Plant Sciences, University of Cambridge, Cambridge, UK.
authors.forename: Betty Y-W
authors.initials: BY
authors.lastname: Chung
authors.affiliation: Schools of Biochemistry and Microbiology, University College Cork, Cork, Ireland Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Atkins
authors.affiliation: Department of Plant Sciences, University of Cambridge, Cambridge, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Carr
authors.affiliation: Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK aef24@cam.ac.uk.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Firth
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D018965:Frameshifting, Ribosomal; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D059014:High-Throughput Nucleotide Sequencing; D016366:Open Reading Frames; D018515:Plant Leaves / Q000821:virology; D017800:Potyvirus / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D014026:Nicotiana / Q000821:virology*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases
keywords: P3N‐PIPO; Potyvirus; RNA virus; gene expression; transcriptional slippage