ArticleGenome research2020
Translation initiation downstream from annotated start codons in human mRNAs coevolves with the Kozak context.
Article in Genome research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 47 citations in OpenAlex.
- Review
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- Protein structure and selection pressure in plants: using mutation to understand the functional importance of protein structure.BMC genomics · 2026Article
- InspectorORF: a tool for visualizing Ribo-Seq and additional genomic or transcriptomic data.Bioinformatics advances · 2026Article
- Alternative start codon selection shapes mitochondrial function and rare human diseases.Molecular cell · 2025Article
- TISCalling: leveraging machine learning to identify translational initiation sites in plants and viruses.Plant molecular biology · 2025Article
- Deep learning tools predict variants in disordered regions with lower sensitivity.BMC genomics · 2025Article
- Structural basis for translational control by the human 48S initiation complex.Nature structural & molecular biology · 2025Article
- Article
- Re-appraising the evidence for the source, regulation and function of p53-family isoforms.Nucleic acids research · 2024Review
- Evaluation of DNA minicircles for delivery of adenine and cytosine base editors using activatable gene on "GO" reporter imaging systems.Molecular therapy. Nucleic acids · 2024Article
- Deep Mutational Scanning in Disease-related Genes with Saturation Mutagenesis-Reinforced Functional Assays (SMuRF).bioRxiv : the preprint server for biology · 2024Article
- Modeling alternative translation initiation sites in plants reveals evolutionarily conservedGenome research · 2024Article
- Alternative Transcripts Diversify Genome Function for Phenome Relevance to Health and Diseases.Genes · 2023Review
- Annotation of uORFs in the OMIM genes allows to reveal pathogenic variants in 5'UTRs.Nucleic acids research · 2023Article
- Distance-dependent inhibition of translation initiation by downstream out-of-frame AUGs is consistent with a Brownian ratchet process of ribosome scanning.Genome biology · 2022Article
- Translation and natural selection of micropeptides from long non-canonical RNAs.Nature communications · 2022Article
- Translational enhancement by base editing of the Kozak sequence rescues haploinsufficiency.Nucleic acids research · 2022Article
- Downstream Alternate Start Site Allows N-Terminal Nonsense Variants to Escape NMD and Results in Functional Recovery by Readthrough and Modulator Combination.Journal of personalized medicine · 2022Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Eukaryotic translation initiation involves preinitiation ribosomal complex 5'-to-3' directional probing of mRNA for codons suitable for starting protein synthesis. The recognition of codons as starts depends on the codon identity and on its immediate nucleotide context known as Kozak context. When the context is weak (i.e., nonoptimal), leaky scanning takes place during which a fraction of ribosomes continues the mRNA probing. We explored the relationship between the context of AUG codons annotated as starts of protein-coding sequences and the next AUG codon occurrence. We found that AUG codons downstream from weak starts occur in the same frame more frequently than downstream from strong starts. We suggest that evolutionary selection on in-frame AUGs downstream from weak start codons is driven by the advantage of the reduction of wasteful out-of-frame product synthesis and also by the advantage of producing multiple proteoforms from certain mRNAs. We confirmed translation initiation downstream from weak start codons using ribosome profiling data. We also tested translation of alternative start codons in 10 specific human genes using reporter constructs. In all tested cases, initiation at downstream start codons was more productive than at the annotated ones. In most cases, optimization of Kozak context did not completely abolish downstream initiation, and in the specific example of
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