ArticleNucleic acids research2020
Gcn2 eIF2α kinase mediates combinatorial translational regulation through nucleotide motifs and uORFs in target mRNAs.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- An upstream open reading frame regulates expression of the mitochondrial protein Slm35 and mitophagy flux.FEBS letters · 2026Article
- eIF3g binding to GUCG boxes located in mRNA coding regions enhances translation of mild heat shock response genes in the yeast Saccharomyces cerevisiae.Nucleic acids research · 2026Article
- The heme-regulated inhibitor kinase Hri1 is activated in response to aminolevulinic acid deficiency in Schizosaccharomyces pombe.PLoS genetics · 2025Article
- Dual Luciferase Reporter Assay in Schizosaccharomyces pombe.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- LINC01615 maintains cell survival in adaptation to nutrient starvation through the pentose phosphate pathway and modulates chemosensitivity in colorectal cancer.Cellular and molecular life sciences : CMLS · 2022Article
- Amino Acid Signaling for TOR in Eukaryotes: Sensors, Transducers, and a Sustainable Agricultural fuTORe.Biomolecules · 2022Review
- FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.Cell death & disease · 2021Article
- Origin of translational control by eIF2α phosphorylation: insights from genome-wide translational profiling studies in fission yeast.Current genetics · 2021Review
- Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.Mechanisms of ageing and development · 2021Article
- Polysome Profiling without Gradient Makers or Fractionation Systems.Journal of visualized experiments : JoVE · 2021Article
- Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.Journal of translational genetics and genomics · 2021Article
- Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias.Frontiers in oncology · 2021Review
- Translational control of coronaviruses.Nucleic acids research · 2020Review
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The protein kinase Gcn2 is a central transducer of nutritional stress signaling important for stress adaptation by normal cells and the survival of cancer cells. In response to nutrient deprivation, Gcn2 phosphorylates eIF2α, thereby repressing general translation while enhancing translation of specific mRNAs with upstream ORFs (uORFs) situated in their 5'-leader regions. Here we performed genome-wide measurements of mRNA translation during histidine starvation in fission yeast Schizosaccharomyces pombe. Polysome analyses were combined with microarray measurements to identify gene transcripts whose translation was up-regulated in response to the stress in a Gcn2-dependent manner. We determined that translation is reprogrammed to enhance RNA metabolism and chromatin regulation and repress ribosome synthesis. Interestingly, translation of intron-containing mRNAs was up-regulated. The products of the regulated genes include additional eIF2α kinase Hri2 amplifying the stress signaling and Gcn5 histone acetyl transferase and transcription factors, together altering genome-wide transcription. Unique dipeptide-coding uORFs and nucleotide motifs, such as '5'-UGA(C/G)GG-3', are found in 5' leader regions of regulated genes and shown to be responsible for translational control.
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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.