ArticleJournal of molecular biology2015
Synonymous codon usage affects the expression of wild type and F508del CFTR.
Article in Journal of molecular biology, 2015. 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, 33 citations in OpenAlex.
- Codon Optimality Modulates Cellular Stress and Innate Immune Responses Triggered by Exogenous RNAs.Journal of molecular biology · 2026Article
- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- Systematic deletion of symmetricalNAR molecular medicine · 2024Article
- Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae.Microbial cell factories · 2024Review
- Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.Human molecular genetics · 2023Article
- Expression of gain-of-function CFTR in cystic fibrosis airway cells restores epithelial function better than wild-type or codon-optimized CFTR.Molecular therapy. Methods & clinical development · 2023Article
- Open reading frame correction using splice-switching antisense oligonucleotides for the treatment of cystic fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Synonymous variants that disrupt messenger RNA structure are significantly constrained in the human population.GigaScience · 2021Article
- Comparative analysis of codon usage betweenMitochondrial DNA. Part B, Resources · 2020Article
- Rare-variant pathogenicity triage and inclusion of synonymous variants improves analysis of disease associations of orphan G protein-coupled receptors.The Journal of biological chemistry · 2019Article
- Different mitogenomic codon usage patterns between damselflies and dragonflies and nine complete mitogenomes for odonates.Scientific reports · 2019Article
- Role for ribosome-associated complex and stress-seventy subfamily B (RAC-Ssb) in integral membrane protein translation.The Journal of biological chemistry · 2017Article
- Alteration of protein function by a silent polymorphism linked to tRNA abundance.PLoS biology · 2017Article
- Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration.Human molecular genetics · 2017Article
- A synonymous codon change alters the drug sensitivity of ΔF508 cystic fibrosis transmembrane conductance regulator.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Codon bias and the folding dynamics of the cystic fibrosis transmembrane conductance regulator.Cellular & molecular biology letters · 2016Review
- Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis.PloS one · 2016Article
- Evidence against resveratrol as a viable therapy for the rescue of defective ΔF508 CFTR.Biochimica et biophysica acta · 2015Article
- Lemur Tyrosine Kinase 2, a novel target in prostate cancer therapy.Oncotarget · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel composed of 1480 amino acids. The major mutation responsible for cystic fibrosis results in loss of amino acid residue, F508 (F508del). Loss of F508 in CFTR alters the folding pathway resulting in endoplasmic-reticulum-associated degradation. This study investigates the role of synonymous codon in the expression of CFTR and CFTR F508del in human HEK293 cells. DNA encoding the open reading frame (ORF) for CFTR containing synonymous codon replacements was expressed using a heterologous vector integrated into the genome. The results indicate that the codon usage greatly affects the expression of CFTR. While the promoter strength driving expression of the ORFs was largely unchanged and the mRNA half-lives were unchanged, the steady-state levels of the mRNA varied by as much as 30-fold. Experiments support that this apparent inconsistency is attributed to nonsense mediated decay independent of exon junction complex. The ratio of CFTR/mRNA indicates that mRNA containing native codons was more efficient in expressing mature CFTR as compared to mRNA containing synonymous high-expression codons. However, when F508del CFTR was expressed after codon optimization, a greater percentage of the protein escaped endoplasmic-reticulum-associated degradation resulting in considerable levels of mature F508del CFTR on the plasma membrane, which showed channel activity. These results indicate that codon usage has an effect on mRNA levels and protein expression, for CFTR, and likely on chaperone-assisted folding pathway, for F508del CFTR.
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