Evidence map›Paper›PMID 34751406›Full record

ArticleNucleic acids research2021

Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting in Theilovirus.

Chris H Hill, Georgia M Cook, Sawsan Napthine, Anuja Kibe, Katherine Brown, Neva Caliskan, Andrew E Firth, Stephen C Graham, Ian Brierley

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
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  3. Molecular architecture and diversity of StopGo/2A translational recoding.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

9 authors at 3 institutions in 2 countries.

Chris H HillDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.ORCID 0000-0001-7037-0611
Georgia M CookDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.ORCID 0000-0003-1577-735X
Sawsan NapthineDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Anuja KibeHelmholtz Institute for RNA-based Infection Research (HIRI), Josef-Schneider-Straße 2/D15, 97080 Würzburg, Germany.
Katherine BrownDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Neva CaliskanHelmholtz Institute for RNA-based Infection Research (HIRI), Josef-Schneider-Straße 2/D15, 97080 Würzburg, Germany.ORCID 0000-0003-0435-4757
Andrew E FirthDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Stephen C GrahamDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.ORCID 0000-0003-4547-4034
Ian BrierleyDivision of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
University of Cambridge · GBHelmholtz Institute for RNA-based Infection Research · DEUniversity of Würzburg · DE

Funding

European Research Council 646891Wellcome Trust 098406/Z/12/BWellcome Trust 106207Wellcome Trust 202797/Z/16/ZWellcome Trust 203864/Z/16/ZWellcome Trust 221818Wellcome Trust 221818/Z/20/Z
6 · The paper itself

Abstract

The 2A protein of Theiler's murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed -1 ribosomal frameshifting (PRF) during infection. Here, we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. We demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence for a pseudoknot-like conformation and suggesting that the recognition of this pseudoknot by beta-shell proteins is a conserved feature in cardioviruses. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of ribosomal pauses around the site of PRF induced by the 2A-pseudoknot complex. Careful normalisation of ribosomal profiling data with a 2A knockout virus facilitated the identification, through disome analysis, of ribosome stacking at the TMEV frameshifting signal. These experiments provide unparalleled detail of the molecular mechanisms underpinning Theilovirus protein-stimulated frameshifting.

Indexed as

Frameshifting, RibosomalRibosomesTheilovirusViral ProteinsViral Proteinsvirus protein 2A

Identifiers

PMID34751406
PMCPMC8599813
OpenAlexW3212900126

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.