ArticleNature communications2024
Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 19 citations in OpenAlex.
- Programmed repair of disease-causing UGA premature termination codons in mammalian brain.Nucleic acids research · 2026Article
- RiboScreenBiomedicines · 2026Review
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- Tetrahedral DNA nanostructure-delivered suppressor tRNA ameliorates nephropathy inNAR molecular medicine · 2026Article
- Anticodon-edited transfer RNAs (ACE-tRNAs) encoded as therapeutic nonviral minimal DNA vectors.Nucleic acids research · 2026Article
- Barriers to the Pharmacologic Rescue of W1282X CFTR.Biochemistry · 2026Article
- AAV-delivered engineered suppressor tRNA rescues visual function in mice with an inherited retinal disease.Nature communications · 2025Article
- Anticodon Edited Transfer RNAs (ACE-tRNAs) Encoded as Therapeutic Nonviral Minimal DNA Vectors.bioRxiv : the preprint server for biology · 2025Article
- Ageing-related decline of translation as a consequence of transcription dysregulation.Journal of the Royal Society, Interface · 2025Article
- Adaptive genetics reveals constraints on protein structure/function by evolving E. coli under constant nutrient limitation.BMC biology · 2025Article
- Identification of translation events that drive nonsense-mediated mRNA decay reveals functional roles for noncoding RNAs.bioRxiv : the preprint server for biology · 2025Article
- High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs.Nucleic acids research · 2025Article
- ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis.Nucleic acids research · 2025Article
- An engineered glutamic acid tRNA for efficient suppression of pathogenic nonsense mutations.Nucleic acids research · 2025Article
- Defining the high-translational readthrough stop codon context.PLoS genetics · 2025Article
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.RNA (New York, N.Y.) · 2025Review
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- Therapeutic Nonsense Suppression Modalities: From Small Molecules to Nucleic Acid-Based Approaches.Biomedicines · 2024Review
- Tuning tRNAs for improved translation.Frontiers in genetics · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Nonsense mutations - the underlying cause of approximately 11% of all genetic diseases - prematurely terminate protein synthesis by mutating a sense codon to a premature stop or termination codon (PTC). An emerging therapeutic strategy to suppress nonsense defects is to engineer sense-codon decoding tRNAs to readthrough and restore translation at PTCs. However, the readthrough efficiency of the engineered suppressor tRNAs (sup-tRNAs) largely varies in a tissue- and sequence context-dependent manner and has not yet yielded optimal clinical efficacy for many nonsense mutations. Here, we systematically analyze the suppression efficacy at various pathogenic nonsense mutations. We discover that the translation velocity of the sequence upstream of PTCs modulates the sup-tRNA readthrough efficacy. The PTCs most refractory to suppression are embedded in a sequence context translated with an abrupt reversal of the translation speed leading to ribosomal collisions. Moreover, modeling translation velocity using Ribo-seq data can accurately predict the suppression efficacy at PTCs. These results reveal previously unknown molecular signatures contributing to genotype-phenotype relationships and treatment-response heterogeneity, and provide the framework for the development of personalized tRNA-based gene therapies.
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Registered trials
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.