Evidence map›Paper›PMID 25676312›Full record

ArticleJournal of molecular biology2015

Synonymous codon usage affects the expression of wild type and F508del CFTR.

Kalpit Shah, Yi Cheng, Brian Hahn, Robert Bridges, Neil A Bradbury, David M Mueller

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Systematic deletion of symmetricalNAR molecular medicine · 2024
    Article
  4. Review
  5. Article
  6. Article
  7. 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 · 2022
    Article
  8. Article
  9. Comparative analysis of codon usage betweenMitochondrial DNA. Part B, Resources · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. 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 · 2016
    Article
  16. Review
  17. Article
  18. Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Kalpit ShahDepartment of Biochemistry and Molecular Biology, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA; Department of Physiology and Biophysics, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA.
Yi ChengDepartment of Physiology and Biophysics, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA.
Brian HahnDepartment of Biochemistry and Molecular Biology, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA.
Robert BridgesDepartment of Physiology and Biophysics, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA.
Neil A BradburyDepartment of Physiology and Biophysics, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA.
David M MuellerDepartment of Biochemistry and Molecular Biology, Rosalind Franklin University, The Chicago Medical School, North Chicago, IL 60064, USA. Electronic address: david.mueller@rosalindfranklin.edu.
Rosalind Franklin University of Medicine and Science · US

Funding

Structure Function of the ATP SynthaseR01GM066223 · NIGMS · ROSALIND FRANKLIN UNIV OF MEDICINE &SCI · PI MUELLER, DAVID MICHAEL · 2002 to 2018
$5.3M
Role of LMTK2 in CFTR TraffickingR01HL102208 · NHLBI · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · PI BRADBURY, NEIL A · 2011 to 2014
$1.5M
Functional expression of CFTR and other multidomain proteinsR21HL094951 · NHLBI · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · PI BRADBURY, NEIL A, MUELLER, DAVID MICHAEL · 2009 to 2010
$424k
NHLBI NIH HHS 1R01HL102208NHLBI NIH HHS R01 HL102208NHLBI NIH HHS R21 HL094951NHLBI NIH HHS R21HL094951NIGMS NIH HHS R01 GM066223NIGMS NIH HHS R01GM066223
6 · The paper itself

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.

Indexed as

Sequence DeletionBlotting, NorthernBlotting, WesternCell MembraneChloridesCodonCystic Fibrosis Transmembrane Conductance RegulatorFluorescent Antibody TechniqueHEK293 CellsHumansMutationOpen Reading FramesProtein FoldingProtein TransportReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionCFTR protein, humanChloridesCodonCystic Fibrosis Transmembrane Conductance RegulatorRNA, MessengerCFTRCFTR F508delnonsense mediated decayprotein foldingsynonymous codon usage

Identifiers

PMID25676312
PMCPMC4355305
OpenAlexW2066010869

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.