Evidence map›Paper›PMID 34871407›Full record

ArticleNucleic acids research2021

Coordination of -1 programmed ribosomal frameshifting by transcript and nascent chain features revealed by deep mutational scanning.

Patrick J Carmody, Matthew H Zimmer, Charles P Kuntz, Haley R Harrington, Kate E Duckworth, Wesley D Penn, Suchetana Mukhopadhyay, Thomas F Miller, Jonathan P Schlebach

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 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. RNAViruses · 2026
    Review
  2. Article
  3. Article
  4. 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
  5. Article
  6. Systematic analysis of nonprogrammed frameshift suppression inProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
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 2 institutions in 1 country.

Patrick J CarmodyDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Matthew H ZimmerDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Charles P KuntzDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Haley R HarringtonDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Kate E DuckworthDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Wesley D PennDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Suchetana MukhopadhyayDepartment of Biology, Indiana University, Bloomington, IN 47405, USA.
Thomas F MillerDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jonathan P SchlebachDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0003-0955-7633
Indiana University Bloomington · USCalifornia Institute of Technology · US

Funding

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
Stimulation of Ribosomal Frameshifting by Cotranslational Membrane Protein Folding and MisfoldingR01GM138845 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI SCHLEBACH, JONATHAN PATRICK · 2021 to 2024
$1.2M
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 AI142383NIGMS NIH HHS R01 GM125063NIGMS NIH HHS R01 GM138845
6 · The paper itself

Abstract

Programmed ribosomal frameshifting (PRF) is a translational recoding mechanism that enables the synthesis of multiple polypeptides from a single transcript. During translation of the alphavirus structural polyprotein, the efficiency of -1PRF is coordinated by a 'slippery' sequence in the transcript, an adjacent RNA stem-loop, and a conformational transition in the nascent polypeptide chain. To characterize each of these effectors, we measured the effects of 4530 mutations on -1PRF by deep mutational scanning. While most mutations within the slip-site and stem-loop reduce the efficiency of -1PRF, the effects of mutations upstream of the slip-site are far more variable. We identify several regions where modifications of the amino acid sequence of the nascent polypeptide impact the efficiency of -1PRF. Molecular dynamics simulations of polyprotein biogenesis suggest the effects of these mutations primarily arise from their impacts on the mechanical forces that are generated by the translocon-mediated cotranslational folding of the nascent polypeptide chain. Finally, we provide evidence suggesting that the coupling between cotranslational folding and -1PRF depends on the translation kinetics upstream of the slip-site. These findings demonstrate how -1PRF is coordinated by features within both the transcript and nascent chain.

Indexed as

Molecular Dynamics SimulationAlphavirusFrameshifting, RibosomalHEK293 CellsHumansKineticsMutationNucleic Acid ConformationPolyproteinsProtein BiosynthesisRibosomesRNA, MessengerRNA, TransferRNA, ViralPolyproteinsRNA, MessengerRNA, TransferRNA, Viral

Identifiers

PMID34871407
PMCPMC8682741
OpenAlexW4225564037

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.