2012
DOI: 10.1073/pnas.1211145109
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Abstract: Programmed −1 ribosomal frameshifting (−1 PRF) is a geneexpression mechanism used to express many viral and some cellular genes. In contrast, efficient natural utilization of −2 PRF has not been demonstrated previously in eukaryotic systems. Like all nidoviruses, members of the Arteriviridae (a family of positive-stranded RNA viruses) express their replicase polyproteins pp1a and pp1ab from two long ORFs (1a and 1b), where synthesis of pp1ab depends on −1 PRF. These polyproteins are posttranslationally cleaved… Show more

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Cited by 206 publications
(288 citation statements)
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References 49 publications
(63 reference statements)
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“…We have provided evidence that the Asc1/RACK1 protein plays a role in reading frame maintenance, a critical feature of translation, and infer that Asc1-mediated cessation of translation is important to avoid synthesis of aberrant proteins through frameshifting, although the precise nature of the frameshifting event (+1 or −2) (Fang et al 2012) that occurs in the asc1-Δ mutant is unknown. Moreover, the effects of the asc1-Δ mutant may be physiologically relevant, since Asc1 protein levels are decreased substantially during hypoxic stress (Bruckmann et al 2009), and since frameshifting is detectable (albeit minimally) at CGA-CGA codon pairs, which are found in 26 yeast genes, with two occurrences of CGA-CGA pairs in one gene (BUD8).…”
Section: Discussionmentioning
confidence: 99%
“…We have provided evidence that the Asc1/RACK1 protein plays a role in reading frame maintenance, a critical feature of translation, and infer that Asc1-mediated cessation of translation is important to avoid synthesis of aberrant proteins through frameshifting, although the precise nature of the frameshifting event (+1 or −2) (Fang et al 2012) that occurs in the asc1-Δ mutant is unknown. Moreover, the effects of the asc1-Δ mutant may be physiologically relevant, since Asc1 protein levels are decreased substantially during hypoxic stress (Bruckmann et al 2009), and since frameshifting is detectable (albeit minimally) at CGA-CGA codon pairs, which are found in 26 yeast genes, with two occurrences of CGA-CGA pairs in one gene (BUD8).…”
Section: Discussionmentioning
confidence: 99%
“…However, more conservative estimations put the mutation rate somewhere between 1.8 and 7 × 10 −3 /nucleotide/year (Chang et al, 2002;Forsberg, 2005), which still places PRRSV among the most rapidly evolving viruses known. Despite the rapidly changing codon sequences of the main ORFs, recently several positionally conserved alternative ORFs have been identified in the PRRSV genome and all of them proved to be protein coding: ORFs partially coding the nsp2TF and nsp2N proteins in the NSP2 region (Fang et al, 2012), ORF5a and ORF2b overlapping with the ORF5 and ORF2a genes (Wu et al, 2001;Firth et al, 2011), respectively. Genome comparison of 46 divergent PRRSV genomes revealed another short ORF in a conserved position, named ORF7a overlapping with the ORF7 gene.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, three accessory proteins were identified translating from fully overlapping ORFs by noncanonical translation mechanisms (Wu et al, 2001;Firth et al, 2011;Fang et al, 2012).…”
mentioning
confidence: 99%
“…Recently, the nsp2 protein, which is coded for by the most variable region of the genome, was demonstrated to be incorporated into virions of several PRRSV strains as a set of differently sized protein isomers (Kappes et al, 2013(Kappes et al, , 2015b. This unexpected result increases the number of viral proteins to at least 10 (full-length nsp2 and its isomers, nsp2TF, E,M,N,ORF5a), that are exposed to the porcine immune system on entry of PRRSV into swine alveolar macrophages (Fang et al, 2012;Veit et al, 2014). The enormous genetic and protein variation of all of these structural proteins, from the least conserved nsp2 to the most conserved M protein shows the complexity and plasticity of the PRRSV genome and virion structure (Rascón-Castelo et al, 2015;Kappes and Faaberg, 2015a).…”
Section: Introductionmentioning
confidence: 99%