ArticleJournal of molecular biology2019
Silencing of Aberrant Secretory Protein Expression by Disease-Associated Mutations.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed.
- Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?Biomedicines · 2026Review
- Human SRP Subunits Coordinate Protein Targeting and mRNA Quality Control.bioRxiv : the preprint server for biology · 2026Article
- Improved functional JAG1 and NOTCH2 variant testing in patients with clinical or suspected Alagille syndrome using new low-Notch activity cells.Human genetics · 2026Article
- Article
- Signal recognition particle-dependent secretome in humans.Scientific reports · 2026Article
- Mechanistic Insights into Protein Biogenesis and Maturation on the Ribosome.Journal of molecular biology · 2025Review
- Multiplex and multimodal mapping of variant effects in secreted proteins via MultiSTEP.Nature structural & molecular biology · 2025Article
- Multiplex, multimodal mapping of variant effects in secreted proteins.bioRxiv : the preprint server for biology · 2025Article
- A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass.Bone research · 2024Article
- Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B.Blood advances · 2024Article
- Loss of Preproinsulin Interaction with Signal Recognition Particle Activates Protein Quality Control, Decreasing mRNA Stability.Journal of molecular biology · 2024Article
- Pathogenic signal peptide variants in the human genome.NAR genomics and bioinformatics · 2023Article
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Specialized Ribosomes in Health and Disease.International journal of molecular sciences · 2023Review
- Aberrant protein targeting activates quality control on the ribosome.Frontiers in cell and developmental biology · 2023Article
- Spf1 and Ste24: quality controllers of transmembrane protein topology in the eukaryotic cell.Frontiers in cell and developmental biology · 2023Review
- Defective Human SRP Induces Protein Quality Control and Triggers Stress Response.Journal of molecular biology · 2022Article
- Targeting of Proteins for Translocation at the Endoplasmic Reticulum.International journal of molecular sciences · 2022Review
- Signal Recognition Particle in Human Diseases.Frontiers in genetics · 2022Article
- Unexpected Implication of SRP and AGO2 in Parkinson's Disease: Involvement in Alpha-Synuclein Biogenesis.Cells · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Signal recognition particle (SRP) recognizes signal sequences of secretory proteins and targets them to the endoplasmic reticulum membrane for translocation. Many human diseases are connected with defects in signal sequences. The current dogma states that the molecular basis of the disease-associated mutations in the secretory proteins is connected with defects in their transport. Here, we demonstrate for several secretory proteins with disease-associated mutations that the molecular mechanism is different from the dogma. Positively charged or helix-breaking mutations in the signal sequence hydrophobic core prevent synthesis of the aberrant proteins and lead to degradation of their mRNAs. The degree of mRNA depletion depends on the location and severity of the mutation in the signal sequence and correlates with inhibition of SRP interaction. Thus, SRP protects secretory protein mRNAs from degradation. The data demonstrate that if disease-associated mutations obstruct SRP interaction, they lead to silencing of the mutated protein expression.
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.