Evidence map›Paper›PMID 32169904›Full record

ArticleThe Journal of biological chemistry2020

Cotranslational folding stimulates programmed ribosomal frameshifting in the alphavirus structural polyprotein.

Haley R Harrington, Matthew H Zimmer, Laura M Chamness, Veronica Nash, Wesley D Penn, Thomas F Miller, Suchetana Mukhopadhyay, Jonathan P Schlebach

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. RNAViruses · 2026
    Review
  3. Article
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  5. Review
  6. Article
  7. Review
  8. Ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Membrane proteins enter the fold.Current opinion in structural biology · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Haley R HarringtonDepartment of Chemistry, Indiana University, Bloomington, Indiana 47405.
Matthew H ZimmerDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125.
Laura M ChamnessDepartment of Chemistry, Indiana University, Bloomington, Indiana 47405.ORCID 0000-0002-3971-2799
Veronica NashDepartment of Chemistry, Indiana University, Bloomington, Indiana 47405.
Wesley D PennDepartment of Chemistry, Indiana University, Bloomington, Indiana 47405.
Thomas F MillerDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125 tfm@caltech.edu.
Suchetana MukhopadhyayDepartment of Biology, Indiana University, Bloomington, Indiana 47405 jschleba@indiana.edu.ORCID 0000-0001-9230-4746
Jonathan P SchlebachDepartment of Chemistry, Indiana University, Bloomington, Indiana 47405 sumukhop@indiana.edu.ORCID 0000-0003-0955-7633
Indiana University Bloomington · USCalifornia Institute of Technology · US

Funding

Undergraduate Research Internships in Pathobiology of Diabetic NephropathyR25DK096999 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BILLY GERALD HUDSON · 2012 to 2026
$1.6M
A New Pradigm for the Rational Expression of Integral Membrane ProteinsR01GM125063 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI CLEMONS, WILLIAM M., MILLER, THOMAS FRANCIS · 2017 to 2020
$1.5M
Topological Heterogeneity as an Evolved Source of Structural Diversity in Viral PolyproteinsR21AI142383 · NIAID · TRUSTEES OF INDIANA UNIVERSITY · PI SCHLEBACH, JONATHAN PATRICK · 2019 to 2020
$413k
NIAID NIH HHS R21 AI142383NIDDK NIH HHS R25 DK096999NIGMS NIH HHS R01 GM125063
6 · The paper itself

Abstract

Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms, including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single mRNA transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work, we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during its biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamics simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results indicate that cotranslational folding of this viral protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent polypeptide chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding or binding events may also stimulate PRF.

Indexed as

Frameshifting, RibosomalProtein BiosynthesisProtein FoldingAlphavirusHEK293 CellsHumansPolyproteinsSindbis VirusViral ProteinsPolyproteinsViral Proteinsalphaviruscotranslational foldingmembrane proteinmembrane protein foldingprogrammed ribosomal frameshiftingprotein foldingribosomeSindbis virustopologytranslation controltranslocationtranslocontransmembrane domain

Identifiers

PMID32169904
PMCPMC7242702
OpenAlexW3012461324

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.