ArticleMolecular and cellular biology1991
Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control.
Article in Molecular and cellular biology, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
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Who cites it
134 citing papers in PubMed, 245 citations in OpenAlex.
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- The Aromatic Amino Acid Biosynthesis GeneMicroorganisms · 2025Article
- Ribosome association inhibits stress-induced gene mRNA localization to stress granules.Genes & development · 2025Article
- CRISPuRe-seq: pooled screening of barcoded ribonucleoprotein reporters reveals regulation of RNA polymerase III transcription by the integrated stress response via mTOR.Nucleic acids research · 2025Article
- Purification and Analysis of eIF2α Phosphorylation by Stress-Activated Protein Kinase Gcn2 from S. cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.Molecular cell · 2024Article
- Research progress on the function and regulatory pathways of amino acid permeases in fungi.World journal of microbiology & biotechnology · 2024Review
- Differential effects of 40S ribosome recycling factors on reinitiation at regulatory uORFs in GCN4 mRNA are not dictated by their roles in bulk 40S recycling.Communications biology · 2024Article
- eIF4F complex dynamics are important for the activation of the integrated stress response.Molecular cell · 2024Article
- Impacts of yeast Tma20/MCTS1, Tma22/DENR and Tma64/eIF2D on translation reinitiation and ribosome recycling.bioRxiv : the preprint server for biology · 2024Article
- The Roles of eIF4G2 in Leaky Scanning and Reinitiation on the Human Dual-Coding POLG mRNA.International journal of molecular sciences · 2023Article
- Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.Antioxidants & redox signaling · 2023Review
- Translational regulation by uORFs and start codon selection stringency.Genes & development · 2023Review
- Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story.RNA (New York, N.Y.) · 2023Review
- The new uORFdb: integrating literature, sequence, and variation data in a central hub for uORF research.Nucleic acids research · 2023Article
- Alternative Transcription Start Site Usage and Functional Implications in Pathogenic Fungi.Journal of fungi (Basel, Switzerland) · 2022Review
- Post-transcriptional regulation during stress.FEMS yeast research · 2022Review
- Article
- Methylated PP2A stabilizes Gcn4 to enable a methionine-induced anabolic program.The Journal of biological chemistry · 2020Article
- Regulation of human sphingomyelin synthase 1 translation through its 5'-untranslated region.FEBS letters · 2020Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GCN4 encodes a transcriptional activator of amino acid-biosynthetic genes in Saccharomyces cerevisiae that is regulated at the translational level by upstream open reading frames (uORFs) in its mRNA leader. uORF4 (counting from the 5' end) is sufficient to repress GCN4 under nonstarvation conditions; uORF1 is required to overcome the inhibitory effect of uORF4 and stimulate GCN4 translation in amino acid-starved cells. Insertions of sequences with the potential to form secondary structure around uORF4 abolish derepression, indicating that ribosomes reach GCN4 by traversing uORF4 sequences rather than by binding internally to the GCN4 start site. By showing that wild-type regulation occurred even when uORF4 was elongated to overlap GCN4 by 130 nucleotides, we provide strong evidence that those ribosomes which translate GCN4 do so by ignoring the uORF4 AUG start codon. This conclusion is in accord with the fact that translation of a uORF4-lacZ fusion was lower in a derepressed gcd1 mutant than in a nonderepressible gcn2 strain. We also show that increasing the distance between uORF1 and uORF4 to the wild-type spacing that separates uORF1 from GCN4 specifically impaired the ability of uORF1 to derepress GCN4 translation. As expected, this alteration led to increased uORF4-lacZ translation in gcd1 cells. Our results suggest that under starvation conditions, a substantial fraction of ribosomes that translate uORF1 fail to reassemble the factors needed for reinitiation by the time they scan to uORF4, but become competent to reinitiate after scanning the additional sequences to GCN4. Under nonstarvation conditions, ribosomes would recover more rapidly from uORF1 translation, causing them all to reinitiate at uORF4 rather than at GCN4.
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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.