ArticleNucleic acids research2023
Precise genome editing of the Kozak sequence enables bidirectional and quantitative modulation of protein translation to anticipated levels without affecting transcription.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Developing a robust multiplex CRISPR/Cas12i3-5M system for trait stacking in soybean.Journal of integrative plant biology · 2026Article
- Kozak sequence libraries for systematically characterizing transgenes across expression levels.Nucleic acids research · 2026Article
- Emergence and evolution of protein-coding de novo genes.Nature reviews. Genetics · 2026Review
- Unlocking the potential of mRNA nanomedicines for comprehensive fibrosis therapy.Molecular therapy. Nucleic acids · 2026Review
- Unlocking translational control of specialized metabolism in plants through 5'UTR structure.Science advances · 2026Article
- Computational Design of an mRNA Vaccine Targeting LRP6 for Triple-Negative Breast Cancer Therapy.Cancer reports (Hoboken, N.J.) · 2026Article
- CRISPR-Cas9-mediated uATG introduction in the 5'UTR of the Uox gene for hyperuricemia mouse models: implications for gout and metabolic disorders.Science China. Life sciences · 2026Article
- Kozak sequences regulate gene expression in Trypanosoma brucei.Nucleic acids research · 2026Article
- cncFinder: A graph-attention-network-based interpretable learning model to identify bifunctional long non-coding RNAs.Molecular therapy. Nucleic acids · 2026Article
- Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.RNA biology · 2025Review
- GC3 codons enhance protein production in diverse GC- and AT-rich plant species.bioRxiv : the preprint server for biology · 2025Article
- RNA elements and their biotechnological applications in plants.The New phytologist · 2025Review
- Article
- Signal Peptides: From Molecular Mechanisms to Applications in Protein and Vaccine Engineering.Biomolecules · 2025Review
- Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Developing mRNA Nanomedicines with Advanced Targeting Functions.Nano-micro letters · 2025Review
- Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence ofInternational journal of molecular sciences · 2024Article
- Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
None of the existing approaches for regulating gene expression can bidirectionally and quantitatively fine-tune gene expression to desired levels. Here, on the basis of precise manipulations of the Kozak sequence, which has a remarkable influence on translation initiation, we proposed and validated a novel strategy to directly modify the upstream nucleotides of the translation initiation codon of a given gene to flexibly alter the gene translation level by using base editors and prime editors. When the three nucleotides upstream of the translation initiation codon (named KZ3, part of the Kozak sequence), which exhibits the most significant base preference of the Kozak sequence, were selected as the editing region to alter the translation levels of proteins, we confirmed that each of the 64 KZ3 variants had a different translation efficiency, but all had similar transcription levels. Using the ranked KZ3 variants with different translation efficiencies as predictors, base editor- and prime editor-mediated mutations of KZ3 in the local genome could bidirectionally and quantitatively fine-tune gene translation to the anticipated levels without affecting transcription in vitro and in vivo. Notably, this strategy can be extended to the whole Kozak sequence and applied to all protein-coding genes in all eukaryotes.
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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.