Evidence map›Paper›PMID 21220547›Full record

ArticleRNA (New York, N.Y.)2011

Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery.

Julie E Takacs, Timothy B Neary, Nicholas T Ingolia, Adesh K Saini, Pilar Martin-Marcos, Jerry Pelletier, Alan G Hinnebusch, Jon R Lorsch

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

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  14. Review
  15. How Ribosomes Translate Cancer.Cancer discovery · 2017
    Review
  16. Review
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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

8 authors at 4 institutions in 2 countries.

Julie E TakacsDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Timothy B Neary
Nicholas T Ingolia
Adesh K Saini
Pilar Martin-Marcos
Jerry Pelletier
Alan G Hinnebusch
Jon R Lorsch
Johns Hopkins University · USNational Institutes of Health · USMcGill University · CAQB3 · US

Funding

Translational & Transcriptional Control Of Gene Expression By Nutrients In YeastZIAHD001004 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI HINNEBUSCH, ALAN G · 2009 to 2025
$34.4M
Small Molecule Effectors of Eukaryotic Translation Initiation Site SelectionR21DK078633 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI LORSCH, JON R. · 2007 to 2008
$446k
Intramural NIH HHSNIDDK NIH HHS DK078633NIDDK NIH HHS R21 DK078633
6 · The paper itself

Abstract

Translation initiation in eukaryotes involves more than a dozen protein factors. Alterations in six factors have been found to reduce the fidelity of start codon recognition by the ribosomal preinitiation complex in yeast, a phenotype referred to as Sui(-). No small molecules are known that affect the fidelity of start codon recognition. Such compounds would be useful tools for probing the molecular mechanics of translation initiation and its regulation. To find compounds with this effect, we set up a high-throughput screen using a dual luciferase assay in S. cerevisiae. Screening of over 55,000 compounds revealed two structurally related molecules that decrease the fidelity of start codon selection by approximately twofold in the dual luciferase assay. This effect was confirmed using additional in vivo assays that monitor translation from non-AUG start codons. Both compounds increase translation of a natural upstream open reading frame previously shown to initiate translation at a UUG. The compounds were also found to exacerbate increased use of UUG as a start codon (Sui(-) phenotype) conferred by haploinsufficiency of wild-type eukaryotic initiation factor (eIF) 1, or by mutation in eIF1. Furthermore, the effects of the compounds are suppressed by overexpressing eIF1, which is known to restore the fidelity of start codon selection in strains harboring Sui(-) mutations in various other initiation factors. Together, these data strongly suggest that the compounds affect the translational machinery itself to reduce the accuracy of selecting AUG as the start codon.

Indexed as

Codon, InitiatorEukaryotic Initiation Factor-1HaploinsufficiencyHeterocyclic CompoundsLuciferasesMutationPeptide Chain Initiation, TranslationalPhenotypeReverse Transcriptase Polymerase Chain ReactionRibosome Subunits, Small, EukaryoticRNA, MessengerSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSmall Molecule LibrariesCodon, InitiatorEukaryotic Initiation Factor-1Heterocyclic CompoundsLuciferasesRNA, MessengerSaccharomyces cerevisiae ProteinsSmall Molecule LibrariesSUI1 protein, S cerevisiae

Identifiers

PMID21220547
PMCPMC3039144
OpenAlexW2147431060

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.