ArticlePLoS biology2016
Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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.
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.
Who cites it
45 citing papers in PubMed, 60 citations in OpenAlex.
- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- Targeting PI3Kγ anchoring enhances CFTR membrane localization and modulator efficacy via PKD1.JCI insight · 2026Article
- General trends in the calnexin-dependent expression and pharmacological rescue of clinical CFTR variants.eLife · 2025Article
- General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants.bioRxiv : the preprint server for biology · 2025Article
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis.Cell insight · 2025Article
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ribosomal Frameshifting Selectively Modulates the Assembly, Function, and Pharmacological Rescue of a Misfolded CFTR Variant.bioRxiv : the preprint server for biology · 2024Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Features of CFTR mRNA and implications for therapeutics development.Frontiers in genetics · 2023Review
- Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy.Frontiers in pharmacology · 2023Article
- Gain- and Loss-of-FunctionCells · 2022Article
- RPLP1, an NS4B-interacting protein, enhances production of CSFV through promoting translation of viral genome.Virulence · 2022Article
- Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.Communications biology · 2022Article
- Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform.CPT: pharmacometrics & systems pharmacology · 2022Article
- Analysis of multiple gene co-expression networks to discover interactions favoring CFTR biogenesis and ΔF508-CFTR rescue.BMC medical genomics · 2021Article
- Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations.Scientific reports · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The most common cystic fibrosis (CF) causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del), results in functional expression defect of the CF transmembrane conductance regulator (CFTR) at the apical plasma membrane (PM) of secretory epithelia, which is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER). Deletion of phenylalanine 670 (ΔF670) in the yeast oligomycin resistance 1 gene (YOR1, an ABC transporter) of Saccharomyces cerevisiae phenocopies the ΔF508-CFTR folding and trafficking defects. Genome-wide phenotypic (phenomic) analysis of the Yor1-ΔF670 biogenesis identified several modifier genes of mRNA processing and translation, which conferred oligomycin resistance to yeast. Silencing of orthologues of these candidate genes enhanced the ΔF508-CFTR functional expression at the apical PM in human CF bronchial epithelia. Although knockdown of RPL12, a component of the ribosomal stalk, attenuated the translational elongation rate, it increased the folding efficiency as well as the conformational stability of the ΔF508-CFTR, manifesting in 3-fold augmented PM density and function of the mutant. Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor) restored the mutant function to ~50% of the wild-type channel in primary CFTRΔF508/ΔF508 human bronchial epithelia. These results and the observation that silencing of other ribosomal stalk proteins partially rescue the loss-of-function phenotype of ΔF508-CFTR suggest that the ribosomal stalk modulates the folding efficiency of the mutant and is a potential therapeutic target for correction of the ΔF508-CFTR folding defect.
Indexed as
Identifiers
What OpenQuestion holds
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.