ArticleNucleic acids research2005
Evolutionary conservation suggests a regulatory function of AUG triplets in 5'-UTRs of eukaryotic genes.
Article in Nucleic acids research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 123 citations in OpenAlex.
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- The birth, death, and evolutionary compensation of uORFs in Drosophila.Nucleic acids research · 2026Article
- The role of untranslated region variants in Mendelian disease: a review.European journal of human genetics : EJHG · 2025Review
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- Translational control of murine adiponectin expression by an upstream open reading frame element.RNA biology · 2023Article
- Short 5' Untranslated Region Enables Optimal Translation of Plant Virus Tricistronic RNA via Leaky Scanning.Journal of virology · 2022Article
- Determinants of genome-wide distribution and evolution of uORFs in eukaryotes.Nature communications · 2021Article
- 5' Untranslated Region Elements Show High Abundance and Great Variability in Homologous ABCA Subfamily Genes.International journal of molecular sciences · 2020Article
- Mammalian Alternative Translation Initiation Is Mostly Nonadaptive.Molecular biology and evolution · 2020Article
- Comprehensive genome-wide identification of angiosperm upstream ORFs with peptide sequences conserved in various taxonomic ranges using a novel pipeline, ESUCA.BMC genomics · 2020Article
- Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs.Journal of molecular biology · 2019Article
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- Translation of upstream open reading frames in a model of neuronal differentiation.BMC genomics · 2019Article
- Quantification and discovery of sequence determinants of protein-per-mRNA amount in 29 human tissues.Molecular systems biology · 2019Article
- Exploring the Role of AUG Triplets in Human Cap-Independent Translation Enhancing Elements.Biochemistry · 2018Article
- Correcting the F508del-CFTR variant by modulating eukaryotic translation initiation factor 3-mediated translation initiation.The Journal of biological chemistry · 2018Article
- The Sugar-Signaling Hub: Overview of Regulators and Interaction with the Hormonal and Metabolic Network.International journal of molecular sciences · 2018Review
- Genome-wide maps of ribosomal occupancy provide insights into adaptive evolution and regulatory roles of uORFs during Drosophila development.PLoS biology · 2018Article
7 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
Funding
Abstract
By comparing sequences of human, mouse and rat orthologous genes, we show that in 5'-untranslated regions (5'-UTRs) of mammalian cDNAs but not in 3'-UTRs or coding sequences, AUG is conserved to a significantly greater extent than any of the other 63 nt triplets. This effect is likely to reflect, primarily, bona fide evolutionary conservation, rather than cDNA annotation artifacts, because the excess of conserved upstream AUGs (uAUGs) is seen in 5'-UTRs containing stop codons in-frame with the start AUG and many of the conserved AUGs are found in different frames, consistent with the location in authentic non-coding sequences. Altogether, conserved uAUGs are present in at least 20-30% of mammalian genes. Qualitatively similar results were obtained by comparison of orthologous genes from different species of the yeast genus Saccharomyces. Together with the observation that mammalian and yeast 5'-UTRs are significantly depleted in overall AUG content, these findings suggest that AUG triplets in 5'-UTRs are subject to the pressure of purifying selection in two opposite directions: the uAUGs that have no specific function tend to be deleterious and get eliminated during evolution, whereas those uAUGs that do serve a function are conserved. Most probably, the principal role of the conserved uAUGs is attenuation of translation at the initiation stage, which is often additionally regulated by alternative splicing in the mammalian 5'-UTRs. Consistent with this hypothesis, we found that open reading frames starting from conserved uAUGs are significantly shorter than those starting from non-conserved uAUGs, possibly, owing to selection for optimization of the level of attenuation.
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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.