title: Switch from cap- to factorless IRES-dependent 0 and +1 frame translation during cellular stress and dicistrovirus infection.
abstract: Internal ribosome entry sites (IRES) are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR) IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A "stop-go" peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Qing S
authors.initials: QS
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Jan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D021901:DNA, Intergenic / Q000235:genetics*; D056629:Dicistroviridae / Q000502:physiology*; D004330:Drosophila / Q000166:cytology; D005796:Genes / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism*; D016364:Reading Frames / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D014777:Virus Diseases / Q000235:genetics* / Q000821:virology
chemical_list: D021901:DNA, Intergenic; D012315:RNA Caps
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