Evidence map›Paper›PMID 34588441›Full record

ArticleNature communications2021

Multiplex suppression of four quadruplet codons via tRNA directed evolution.

Erika A DeBenedictis, Gavriela D Carver, Christina Z Chung, Dieter Söll, Ahmed H Badran

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 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  7. BeyondChemical reviews · 2025
    Review
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  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Tuning tRNAs for improved translation.Frontiers in genetics · 2024
    Review
  16. Review
  17. Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023
    Review
  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 at 2 institutions in 1 country.

Erika A DeBenedictis *The Broad Institute of MIT & Harvard, Cambridge, MA, USA.ORCID 0000-0002-7933-2651
Gavriela D Carver *The Broad Institute of MIT & Harvard, Cambridge, MA, USA.ORCID 0000-0001-9371-4157
Christina Z ChungDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.ORCID 0000-0001-7761-8165
Dieter SöllDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.ORCID 0000-0002-3077-8986
Ahmed H BadranThe Broad Institute of MIT & Harvard, Cambridge, MA, USA. ahbadran@scripps.edu.ORCID 0000-0002-8105-1883
Broad Institute · USYale University · US

Funding

Studies of Transfer RNAR35GM122560 · NIGMS · YALE UNIVERSITY · PI SOLL, DIETER · 2017 to 2022
$5.6M
Functional Interrogation Of Ribosomal Biology Using Continuous EvolutionDP5OD024590 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI BADRAN, AHMED HUSSEIN · 2017 to 2021
$2.2M
Quadruplet Decoding for Multiplexed Non-Canonical Amino Acid IncorporationF31AI145181 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DEBENEDICTIS, ERIKA ALDEN · 2019 to 2020
$88k
NIAID NIH HHS F31 AI145181NIGMS NIH HHS R35 GM122560NIH HHS DP5 OD024590
6 · The paper itself

Abstract

Genetic code expansion technologies supplement the natural codon repertoire with assignable variants in vivo, but are often limited by heterologous translational components and low suppression efficiencies. Here, we explore engineered Escherichia coli tRNAs supporting quadruplet codon translation by first developing a library-cross-library selection to nominate quadruplet codon-anticodon pairs. We extend our findings using a phage-assisted continuous evolution strategy for quadruplet-decoding tRNA evolution (qtRNA-PACE) that improved quadruplet codon translation efficiencies up to 80-fold. Evolved qtRNAs appear to maintain codon-anticodon base pairing, are typically aminoacylated by their cognate tRNA synthetases, and enable processive translation of adjacent quadruplet codons. Using these components, we showcase the multiplexed decoding of up to four unique quadruplet codons by their corresponding qtRNAs in a single reporter. Cumulatively, our findings highlight how E. coli tRNAs can be engineered, evolved, and combined to decode quadruplet codons, portending future developments towards an exclusively quadruplet codon translation system.

Indexed as

Directed Molecular EvolutionAmino AcidsAmino Acyl-tRNA SynthetasesAnticodonCloning, MolecularCodonEscherichia coliEscherichia coli ProteinsProtein BiosynthesisRNA, BacterialRNA, TransferAmino AcidsAmino Acyl-tRNA SynthetasesAnticodonCodonEscherichia coli ProteinsRNA, BacterialRNA, Transfer

Identifiers

PMID34588441
PMCPMC8481270
OpenAlexW3202524566

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.