Evidence map›Paper›PMID 34887415›Full record

ArticleNature communications2021

Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch.

Chris H Hill, Lukas Pekarek, Sawsan Napthine, Anuja Kibe, Andrew E Firth, Stephen C Graham, Neva Caliskan, Ian Brierley

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

8 authors at 4 institutions in 2 countries.

Chris H Hill *Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. chris.hill@york.ac.uk.ORCID http://orcid.org/0000-0001-7037-0611
Lukas Pekarek *Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.
Sawsan Napthine *Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Anuja KibeHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.ORCID http://orcid.org/0000-0001-8547-785X
Andrew E FirthDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.ORCID http://orcid.org/0000-0002-7986-9520
Stephen C GrahamDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. scg34@cam.ac.uk.ORCID http://orcid.org/0000-0003-4547-4034
Neva CaliskanHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany. neva.caliskan@helmholtz-hiri.de.ORCID http://orcid.org/0000-0003-0435-4757
Ian BrierleyDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. ib103@cam.ac.uk.
University of Cambridge · GBHelmholtz Centre for Infection Research · DEMRC Laboratory of Molecular Biology · GBUniversity of Würzburg · DE

Funding

Biotechnology and Biological Sciences Research Council BB/D009499/1Medical Research Council MC_U105184332Wellcome Trust 221818Wellcome Trust WT096570Wellcome Trust (Wellcome) 098406/Z/12/BWellcome Trust (Wellcome) 106207/Z/14/ZWellcome Trust (Wellcome) 202797/Z/16/ZWellcome Trust (Wellcome) 221818/Z/20/Z
6 · The paper itself

Abstract

Programmed -1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we present the X-ray crystal structure of 2A and show that it selectively binds to a pseudoknot-like conformation of the PRF stimulatory RNA element in the viral genome. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, likely explaining the increase in PRF efficiency in the presence of 2A. Next, we demonstrate a strong interaction between 2A and the small ribosomal subunit and present a cryo-EM structure of 2A bound to initiated 70S ribosomes. Multiple copies of 2A bind to the 16S rRNA where they may compete for binding with initiation and elongation factors. Together, these results define the structural basis for RNA recognition by 2A, show how 2A-mediated stabilisation of an RNA pseudoknot promotes PRF, and reveal how 2A accumulation may shut down translation during virus infection.

Indexed as

Gene Expression Regulation, ViralCardiovirus InfectionsCrystallography, X-RayEncephalomyocarditis virusFrameshifting, RibosomalHumansRibosomesViral ProteinsViral Proteinsvirus protein 2A

Identifiers

PMID34887415
PMCPMC8660796
OpenAlexW4226021160

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.