Evidence map›Paper›PMID 33290521›Full record

ArticleNucleic acids research2021

A suppressor tRNA-mediated feedforward loop eliminates leaky gene expression in bacteria.

Joanne M L Ho, Corwin A Miller, Sydney E Parks, Jacob R Mattia, Matthew R Bennett

Abstract 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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Pulsatile basal gene expression as a fitness determinant in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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

5 authors.

Joanne M L HoDepartment of Biosciences, Rice University MS-140, 6100 Main St., Houston, TX 77005, USA.
Corwin A MillerDepartment of Biosciences, Rice University MS-140, 6100 Main St., Houston, TX 77005, USA.
Sydney E ParksDepartment of Biosciences, Rice University MS-140, 6100 Main St., Houston, TX 77005, USA.
Jacob R MattiaDepartment of Biosciences, Rice University MS-140, 6100 Main St., Houston, TX 77005, USA.
Matthew R BennettDepartment of Biosciences, Rice University MS-140, 6100 Main St., Houston, TX 77005, USA.

Funding

Expanding the utility of transcriptional bacterial computingR01GM117138 · NIGMS · RICE UNIVERSITY · PI BENNETT, MATTHEW R., JOSIC, KRESIMIR · 2016 to 2019
$2.0M
NIGMS NIH HHS R01 GM117138
6 · The paper itself

Abstract

Ligand-inducible genetic systems are the mainstay of synthetic biology, allowing gene expression to be controlled by the presence of a small molecule. However, 'leaky' gene expression in the absence of inducer remains a persistent problem. We developed a leak dampener tool that drastically reduces the leak of inducible genetic systems while retaining signal in Escherichia coli. Our system relies on a coherent feedforward loop featuring a suppressor tRNA that enables conditional readthrough of silent non-sense mutations in a regulated gene, and this approach can be applied to any ligand-inducible transcription factor. We demonstrate proof-of-principle of our system with the lactate biosensor LldR and the arabinose biosensor AraC, which displayed a 70-fold and 630-fold change in output after induction of a fluorescence reporter, respectively, without any background subtraction. Application of the tool to an arabinose-inducible mutagenesis plasmid led to a 540-fold change in its output after induction, with leak decreasing to the level of background mutagenesis. This study provides a modular tool for reducing leak and improving the fold-induction within genetic circuits, demonstrated here using two types of biosensors relevant to cancer detection and genetic engineering.

Indexed as

Gene Expression Regulation, BacterialArabinoseAraC Transcription FactorCodon, TerminatorDNA-Binding ProteinsEscherichia coliEscherichia coli ProteinsLactic AcidMutagenesisPlasmidsProtein BiosynthesisRNA, CatalyticRNA, TransferTranscription FactorsArabinoseAraC protein, E coliAraC Transcription FactorCodon, TerminatorDNA-Binding ProteinsEscherichia coli Proteinshammerhead ribozymeLactic AcidLldR protein, E coliRNA, CatalyticRNA, TransferTranscription Factors

Identifiers

PMID33290521
PMCPMC7969014

What OpenQuestion holds

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LicenceCC BY
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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.