ArticleRNA (New York, N.Y.)2011
Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery.
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.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Mechanosensor-mediated Hsp70 phosphorylation orchestrates the landscape of the heat shock response.Nature communications · 2025Article
- Unexpected molecular mechanism of Orc6-based Meier-Gorlin syndrome: insights from a humanized Drosophila model.Genetics · 2025Article
- Deciphering the landscape of cis-acting sequences in natural yeast transcript leaders.Nucleic acids research · 2025Article
- Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelity.PLoS genetics · 2024Article
- Conserved 5-methyluridine tRNA modification modulates ribosome translocation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RiboScreenInternational journal of molecular sciences · 2024Article
- Deciphering thebioRxiv : the preprint server for biology · 2024Article
- Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelity.bioRxiv : the preprint server for biology · 2024Article
- SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA.PLoS pathogens · 2024Article
- The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions.Molecular cell · 2023Article
- Article
- Prevalence of alternative AUG and non-AUG translation initiators and their regulatory effects across plants.Genome research · 2020Article
- Temperature-dependent regulation of upstream open reading frame translation in S. cerevisiae.BMC biology · 2019Article
- Cancer Biogenesis in Ribosomopathies.Cells · 2019Review
- How Ribosomes Translate Cancer.Cancer discovery · 2017Review
- Non-AUG translation: a new start for protein synthesis in eukaryotes.Genes & development · 2017Review
- Article
- Article
- The mammalian orthoreovirus bicistronic M3 mRNA initiates translation using a 5' end-dependent, scanning mechanism that does not require interaction of 5'-3' untranslated regions.Virus research · 2014Article
- Conserved residues in yeast initiator tRNA calibrate initiation accuracy by regulating preinitiation complex stability at the start codon.Genes & development · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
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.
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Registered trials
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.