ArticlePLoS genetics2014
Ribosomal readthrough at a short UGA stop codon context triggers dual localization of metabolic enzymes in Fungi and animals.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 142 citations in OpenAlex.
- Release factor 3 degradation enhances aminoglycoside-mediated translational readthrough at MECP2 nonsense mutations.Journal of molecular medicine (Berlin, Germany) · 2026Article
- RNAViruses · 2026Review
- Genomic stop codon scanning reveals quantitative principles of nonsense-mediated mRNA decay.bioRxiv : the preprint server for biology · 2025Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- Defining the high-translational readthrough stop codon context.PLoS genetics · 2025Article
- The impact of phenotypic heterogeneity on fungal pathogenicity and drug resistance.FEMS microbiology reviews · 2025Review
- A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2.The Journal of cell biology · 2024Article
- Calorie restriction and rapamycin distinctly restore non-canonical ORF translation in the muscles of aging mice.NPJ Regenerative medicine · 2024Article
- Hominini-specific regulation of the cell cycle by stop codon readthrough of FEM1B.Journal of cell science · 2024Article
- Environment modulates protein heterogeneity through transcriptional and translational stop codon readthrough.Nature communications · 2024Article
- Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations.Journal of molecular medicine (Berlin, Germany) · 2024Article
- A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase.bioRxiv : the preprint server for biology · 2024Article
- The RNA world of fungal pathogens.PLoS pathogens · 2023Article
- Evolution of termination codons of proteins and the TAG-TGA paradox.Scientific reports · 2023Article
- A high-quality reference genome for the fission yeast Schizosaccharomyces osmophilus.G3 (Bethesda, Md.) · 2023Article
- Distal nucleotides affect the rate of stop codon read-through.Quantitative biology (Beijing, China) · 2023Article
- Monitoring translation in all reading frames downstream of weak stop codons provides mechanistic insights into the impact of nucleotide and cellular contexts.Nucleic acids research · 2023Article
- Computational Evaluation of Peroxisomal Targeting Signals in Metazoa.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Phenotypic mutations contribute to protein diversity and shape protein evolution.Protein science : a publication of the Protein Society · 2022Review
- NanoLuc reporters identifyiScience · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB) and NAD-dependent malate dehydrogenase 1 (MDH1) that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1). Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated.
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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.