Evidence map›Paper›PMID 26999002›Full record

ArticleNature methods2016

Reprogramming eukaryotic translation with ligand-responsive synthetic RNA switches.

Andrew V Anzalone, Annie J Lin, Sakellarios Zairis, Raul Rabadan, Virginia W Cornish

Abstract read
In one paragraph

Article in Nature methods, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Recent advances in therapeutic gene-editing technologies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  6. Article
  7. Riboswitches, from cognition to transformation.Synthetic and systems biotechnology · 2023
    Review
  8. Prime Editing: An All-Rounder for Genome Editing.International journal of molecular sciences · 2022
    Review
  9. Article
  10. Review
  11. Article
  12. Aptamers, Riboswitches, and Ribozymes inLife (Basel, Switzerland) · 2021
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

5 authors at 1 institution in 1 country.

Andrew V AnzaloneDepartment of Chemistry, Columbia University, New York, New York, USA.
Annie J LinDepartment of Chemistry, Columbia University, New York, New York, USA.
Sakellarios ZairisDepartment of Systems Biology, Columbia University, New York, New York, USA.
Raul RabadanDepartment of Systems Biology, Columbia University, New York, New York, USA.
Virginia W CornishDepartment of Chemistry, Columbia University, New York, New York, USA.
Columbia University · US

Funding

Topology of Cancer Evolution and HeterogeneityU54CA193313 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IAVARONE, ANTONIO, RABADAN, RAUL · 2015 to 2020
$10.4M
A Household Yeast Biosensor for CholeraR01AI110794 · NIAID · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI CORNISH, VIRGINIA W · 2015 to 2019
$3.2M
Mechanistic Basis for Amino Acid Discrimination by the Translational MachineryR01GM090126 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI CORNISH, VIRGINIA W · 2010 to 2013
$1.5M
Clinical and Translational Science AwardTL1TR000082 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$732k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
Unnatural Amino Acid Mutagenesis with Fluorescent Amino AcidsF30CA174357 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANZALONE, ANDREW VITO · 2013 to 2016
$179k
NCATS NIH HHS TL1 TR000082NCI NIH HHS F30 CA174357NCI NIH HHS U54 CA193313NCRR NIH HHS S10 RR027050NIAID NIH HHS R01 AI110794NIGMS NIH HHS R01 GM090126
6 · The paper itself

Abstract

Protein synthesis in eukaryotes is regulated by diverse reprogramming mechanisms that expand the coding capacity of individual genes. Here, we exploit one such mechanism, termed -1 programmed ribosomal frameshifting (-1 PRF), to engineer ligand-responsive RNA switches that regulate protein expression. First, efficient -1 PRF stimulatory RNA elements were discovered by in vitro selection; then, ligand-responsive switches were constructed by coupling -1 PRF stimulatory elements to RNA aptamers using rational design and directed evolution in Saccharomyces cerevisiae. We demonstrate that -1 PRF switches tightly control the relative stoichiometry of two distinct protein outputs from a single mRNA, exhibiting consistent ligand response across whole populations of cells. Furthermore, -1 PRF switches were applied to build single-mRNA logic gates and an apoptosis module in yeast. Together, these results showcase the potential for harnessing translation-reprogramming mechanisms for synthetic biology, and they establish -1 PRF switches as powerful RNA tools for controlling protein synthesis in eukaryotes.

Indexed as

BiotechnologyCellular ReprogrammingDirected Molecular EvolutionFrameshifting, RibosomalGene Expression Regulation, FungalLigandsProtein BiosynthesisRiboswitchRNA, FungalRNA, MessengerSaccharomyces cerevisiaeLigandsRiboswitchRNA, FungalRNA, Messenger

Identifiers

PMID26999002
PMCPMC4850110
OpenAlexW2302027613

What OpenQuestion holds

Textmetadata
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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.