ArticleProceedings of the National Academy of Sciences of the United States of America2012
Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers.
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Who cites it
194 citing papers in PubMed, 293 citations in OpenAlex.
- Heterodimerization of PRRSV replicase membrane proteins nsp2 and nsp3 regulates their cytoplasmic tail binding to viral RdRp domain for sgRNA synthesis.Journal of virology · 2026Article
- Emergence of a Novel Porcine Reproductive and Respiratory Syndrome Virus 2 Strain Recombined from Two Modified Live Virus-like Strains and Its Pathogenicity for Piglets.Animals : an open access journal from MDPI · 2026Article
- FScanR reveals widespread programmed ribosomal frameshifting consistent with neutral evolution in a ciliate model.European journal of protistology · 2026Article
- Porcine reproductive and respiratory syndrome virus antagonizes the host restriction factor SHFL to sustain viral programmed ribosomal frameshifting and replication.Journal of virology · 2026Article
- Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The biological functions of PRRSV nonstructural protein NSP2 in viral infection and replication and its role in host regulatory mechanisms.Frontiers in veterinary science · 2026Review
- Genetic and Pathogenic Characteristics of Novel PRRSV-1 Strain CH-JX-2504 and CH-SDTA-2506 in China.Transboundary and emerging diseases · 2026Article
- RNA Structural Ensemble Determinants of -1 Programmed Ribosomal Frameshifting Efficiency Across Coronavirus Evolution.Journal of molecular biology · 2025Article
- Mass Spectrometry-Based Proteomic Analysis of Porcine Reproductive and Respiratory Syndrome Virus NSP9 Protein with Host Proteins.Animals : an open access journal from MDPI · 2025Article
- Cytoplasmic translocation of tripartite motif-containing 28 is critical for PRRSV-induced autophagy through promoting Vps34-Beclin1 complex formation.Journal of virology · 2025Article
- In Vitro Characterization of Vaccine Strain-like Porcine Reproductive and Respiratory Syndrome Virus Strains Isolated from Weaned Pigs Exhibiting Respiratory Symptoms.Pathogens (Basel, Switzerland) · 2025Article
- Nsp2 replicase-mediated viral uncoating in porcine alveolar macrophages contributes to the attenuation of PRRSV-2 live attenuated vaccine.Journal of virology · 2025Article
- LGALS3BP/90K suppresses porcine reproductive and respiratory syndrome virus replication by enhancing GP3 degradation and stimulating innate immunity.Veterinary research · 2025Article
- Strategies and scheming: the war between PRRSV and host cells.Virology journal · 2025Review
- Etiological Detection, Isolation, and Pathogenicity of Porcine Reproductive and Respiratory Syndrome Virus in China.Veterinary sciences · 2025Article
- The dimeric conformation of PRRSV nsp1α is important for its ability to regulate viral RNA synthesis.Veterinary research · 2025Article
- Article
- Giant RNA genomes: Roles of host, translation elongation, genome architecture, and proteome in nidoviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Research Progress on the GP3 Protein of Porcine Reproductive and Respiratory Syndrome Virus.Animals : an open access journal from MDPI · 2025Review
- The full-length nsp2 replicase contributes to viral assembly in highly pathogenic PRRSV-2.Journal of virology · 2025Article
134 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 5 countries.
Funding
Abstract
Programmed -1 ribosomal frameshifting (-1 PRF) is a gene-expression 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 into at least 13 functional nonstructural proteins. Here we report that porcine reproductive and respiratory syndrome virus (PRRSV), and apparently most other arteriviruses, use an additional PRF mechanism to access a conserved alternative ORF that overlaps the nsp2-encoding region of ORF1a in the +1 frame. We show here that this ORF is translated via -2 PRF at a conserved G_GUU_UUU sequence (underscores separate ORF1a codons) at an estimated efficiency of around 20%, yielding a transframe fusion (nsp2TF) with the N-terminal two thirds of nsp2. Expression of nsp2TF in PRRSV-infected cells was verified using specific Abs, and the site and direction of frameshifting were determined via mass spectrometric analysis of nsp2TF. Further, mutagenesis showed that the frameshift site and an unusual frameshift-stimulatory element (a conserved CCCANCUCC motif 11 nucleotides downstream) are required to direct efficient -2 PRF. Mutations preventing nsp2TF expression impair PRRSV replication and produce a small-plaque phenotype. Our findings demonstrate that -2 PRF is a functional gene-expression mechanism in eukaryotes and add another layer to the complexity of arterivirus genome expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.