ArticlePLoS biology2017
Alteration of protein function by a silent polymorphism linked to tRNA abundance.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled it
- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- Evidence for Non-optimal Codon Choice in Highly Transcribed Sex-Biased Genes of Drosophila melanogaster.Genome biology and evolution · 2026Article
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- Large variations in total and allele-specific transcript expression in a disease mutation-independent manner.Scientific reports · 2026Article
- Rethinking RNA Modifications: Therapeutic Strategies for Targeting Dysregulated RNA.Journal of molecular biology · 2025Review
- ADARs: pleiotropy in function, versatility in application.Nucleic acids research · 2025Review
- A generative language model decodes contextual constraints on codon choice for mRNA design.bioRxiv : the preprint server for biology · 2025Article
- Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes.Science (New York, N.Y.) · 2024Article
- Disruption of tRNA biogenesis enhances proteostatic resilience, improves later-life health, and promotes longevity.PLoS biology · 2024Article
- The Effects of Codon Usage on Protein Structure and Folding.Annual review of biophysics · 2024Review
- Integrated multiplexed assays of variant effect reveal determinants of catechol-O-methyltransferase gene expression.Molecular systems biology · 2024Article
- Evolving precision: rRNA expansion segment 7S modulates translation velocity and accuracy in eukaryal ribosomes.Nucleic acids research · 2024Article
- Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations.Nature communications · 2024Article
- Pan-cellular organelles and suborganelles-from common functions to cellular diversity?Genes & development · 2024Review
- Identification and mechanism determination of the efflux pump subunit amrB gene mutations linked to gentamicin susceptibility in clinical Burkholderia pseudomallei from Malaysian Borneo.Molecular genetics and genomics : MGG · 2024Article
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- Codon-optimization in gene therapy: promises, prospects and challenges.Frontiers in bioengineering and biotechnology · 2024Review
- Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery.Nucleic acids research · 2023Article
- Two co-inherited SNPs of the telomerase reverse transcriptase (TERT) gene are associated with Iraqi patients with lung cancer.Journal of medical biochemistry · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for protein function, as by definition they exchange only codons, not amino acids. We identified an sSNP that modifies the local translation speed of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stability and function. This sSNP introduces a codon pairing to a low-abundance tRNA that is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting tissue-specific effects of this sSNP. Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of the sSNP and rescues protein conformation and function. Our results highlight the wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA translation and provide direct evidence for the central role of cellular tRNA levels in mediating the actions of sSNPs in a tissue-specific manner.
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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.