ArticleRNA (New York, N.Y.)2014
A single inhibitory upstream open reading frame (uORF) is sufficient to regulate Candida albicans GCN4 translation in response to amino acid starvation conditions.
Article in RNA (New York, N.Y.), 2014. 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, 37 citations in OpenAlex.
- Ribo-ITP enables identification of translons from limited input samples.Nature communications · 2026Article
- Comprehensive mapping of the 5' and 3' untranslated regions ofRNA (New York, N.Y.) · 2026Article
- Research progress on the function and regulatory pathways of amino acid permeases in fungi.World journal of microbiology & biotechnology · 2024Review
- Translational regulation by uORFs and start codon selection stringency.Genes & development · 2023Review
- Relationships between Secreted Aspartyl Proteinase 2 and General Control Nonderepressible 4 gene in the Candida albicans resistant to itraconazole under planktonic and biofilm conditions.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- 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
- Impact of uORFs in mediating regulation of translation in stress conditions.BMC molecular and cell biology · 2021Article
- Ethylzingerone, a Novel Compound with Antifungal Activity.Antimicrobial agents and chemotherapy · 2021Article
- A Conserved Gcn2-Gcn4 Axis Links Methionine Utilization and the Oxidative Stress Response inFrontiers in fungal biology · 2021Article
- Global translational landscape of the Candida albicans morphological transition.G3 (Bethesda, Md.) · 2021Article
- Quantitative global studies reveal differential translational control by start codon context across the fungal kingdom.Nucleic acids research · 2020Article
- THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans.International journal of molecular medicine · 2018Article
- Molecular and Physiological Study ofProteomes · 2018Review
- The 5' Untranslated Region of themSphere · 2018Article
- Please do not recycle! Translation reinitiation in microbes and higher eukaryotes.FEMS microbiology reviews · 2018Review
- General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Farnesol inhibits translation to limit growth and filamentation inMicrobial cell (Graz, Austria) · 2017Article
- In vivo evidence that eIF3 stays bound to ribosomes elongating and terminating on short upstream ORFs to promote reinitiation.Nucleic acids research · 2017Article
- Control of Candida albicans morphology and pathogenicity by post-transcriptional mechanisms.Cellular and molecular life sciences : CMLS · 2016Review
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Candida albicans is a major fungal pathogen that responds to various environmental cues as part of its infection mechanism. We show here that the expression of C. albicans GCN4, which encodes a transcription factor that regulates morphogenetic and metabolic responses, is translationally regulated in response to amino acid starvation induced by exposure to the histidine analog 3-aminotriazole (3AT). However, in contrast to the well-known translational control mechanisms that regulate yeast GCN4 and mammalian ATF4 expression via multiple upstream open reading frames (uORFs) in their 5'-leader sequences, a single inhibitory uORF is necessary and sufficient for C. albicans GCN4 translational control. The 5'-leader sequence of GCN4 contains three uORFs, but uORF3 alone is sufficient for translational regulation. Under nonstress conditions, uORF3 inhibits GCN4 translation. Amino acid starvation conditions promote Gcn2-mediated phosphorylation of eIF2α and leaky ribosomal scanning to bypass uORF3, inducing GCN4 translation. GCN4 expression is also transcriptionally regulated, although maximal induction is observed at higher concentrations of 3AT compared with translational regulation. C. albicans GCN4 expression is therefore highly regulated by both transcriptional and translational control mechanisms. We suggest that it is particularly important that Gcn4 levels are tightly controlled since Gcn4 regulates morphogenetic changes during amino acid starvation conditions, which are important determinants of virulence in this fungus.
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