Evidence map›Paper›PMID 24825891›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Transactivation of programmed ribosomal frameshifting by a viral protein.

Yanhua Li, Emmely E Treffers, Sawsan Napthine, Ali Tas, Longchao Zhu, Zhi Sun, Susanne Bell, Brian L Mark, Peter A van Veelen, Martijn J van Hemert and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
11.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 164 citations in OpenAlex.

  1. Article
  2. Article
  3. 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 · 2026
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  11. 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 · 2025
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  12. Review
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45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 4 countries.

Yanhua LiDepartment of Veterinary and Biomedical Sciences and Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007;Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506;
Emmely E TreffersMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;
Sawsan NapthineDivision of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and.
Ali TasMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;
Longchao ZhuDepartment of Veterinary and Biomedical Sciences and Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007;Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506;
Zhi SunDepartment of Veterinary and Biomedical Sciences and Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007;
Susanne BellDivision of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and.
Brian L MarkDepartment of Microbiology, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
Peter A van VeelenDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;
Martijn J van HemertMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;
Andrew E FirthDivision of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and.
Ian BrierleyDivision of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and yfang@vet.k-state.edu ib103@mole.bio.cam.ac.uk e.j.snijder@lumc.nl.
Eric J SnijderMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands; yfang@vet.k-state.edu ib103@mole.bio.cam.ac.uk e.j.snijder@lumc.nl.
Ying FangDepartment of Veterinary and Biomedical Sciences and Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007;Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506; yfang@vet.k-state.edu ib103@mole.bio.cam.ac.uk e.j.snijder@lumc.nl.
Leiden University Medical Center · NLUniversity of Cambridge · GBKansas State University · USSouth Dakota State University · USUniversity of Manitoba · CA

Funding

Biotechnology and Biological Sciences Research Council BB/G008205/1Wellcome TrustWellcome Trust 088789
6 · The paper itself

Abstract

Programmed -1 ribosomal frameshifting (-1 PRF) is a widely used translational mechanism facilitating the expression of two polypeptides from a single mRNA. Commonly, the ribosome interacts with an mRNA secondary structure that promotes -1 frameshifting on a homopolymeric slippery sequence. Recently, we described an unusual -2 frameshifting (-2 PRF) signal directing efficient expression of a transframe protein [nonstructural protein 2TF (nsp2TF)] of porcine reproductive and respiratory syndrome virus (PRRSV) from an alternative reading frame overlapping the viral replicase gene. Unusually, this arterivirus PRF signal lacks an obvious stimulatory RNA secondary structure, but as confirmed here, can also direct the occurrence of -1 PRF, yielding a third, truncated nsp2 variant named "nsp2N." Remarkably, we now show that both -2 and -1 PRF are transactivated by a protein factor, specifically a PRRSV replicase subunit (nsp1β). Embedded in nsp1β's papain-like autoproteinase domain, we identified a highly conserved, putative RNA-binding motif that is critical for PRF transactivation. The minimal RNA sequence required for PRF was mapped within a 34-nt region that includes the slippery sequence and a downstream conserved CCCANCUCC motif. Interaction of nsp1β with the PRF signal was demonstrated in pull-down assays. These studies demonstrate for the first time, to our knowledge, that a protein can function as a transactivator of ribosomal frameshifting. The newly identified frameshifting determinants provide potential antiviral targets for arterivirus disease control and prevention. Moreover, protein-induced transactivation of frameshifting may be a widely used mechanism, potentially including previously undiscovered viral strategies to regulate viral gene expression and/or modulate host cell translation upon infection.

Indexed as

AnimalsCell LineChromatography, LiquidElectrophoresis, Polyacrylamide GelFrameshifting, RibosomalGene Expression Regulation, ViralHaplorhiniHEK293 CellsHumansImmunoassayLuciferasesPorcine respiratory and reproductive syndrome virusRosaniline DyesTandem Mass SpectrometryTranscriptional ActivationViral Nonstructural Proteinscoomassie Brilliant BlueLuciferasesRosaniline DyesViral Nonstructural Proteinsgenetic recodingnsp1betatranslational control

Identifiers

PMID24825891
PMCPMC4040542
OpenAlexW2045265165

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.