ArticleNature communications2021
C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- CaNature cell biology · 2025Article
- Zinc finger domains bind low-complexity domain polymers.Nature communications · 2025Article
- NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.Communications biology · 2025Article
- C9orf72 polyPR interaction with the nuclear pore complex.Biophysical journal · 2024Article
- Cross-Effects in Folding and Phase Transitions of hnRNP A1 and C9Orf72 RNA G4 In Vitro.Molecules (Basel, Switzerland) · 2024Article
- Reversal ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The nuclear import receptor Kapβ2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.Communications biology · 2024Article
- Article
- Sulfated disaccharide protects membrane and DNA damages from arginine-rich dipeptide repeats in ALS.Science advances · 2024Article
- Enzymatic and synthetic regulation of polypeptide folding.Chemical science · 2024Review
- Validated assays for the quantification of C9orf72 human pathology.Scientific reports · 2024Article
- Pectolinarigenin Improves Oxidative Stress and Apoptosis in Mouse NSC-34 Motor Neuron Cell Lines Induced by C9-ALS-Associated Proline-Arginine Dipeptide Repeat Proteins by Enhancing Mitochondrial Fusion Mediated via the SIRT3/OPA1 Axis.Antioxidants (Basel, Switzerland) · 2023Article
- Nuclear transport proteins: structure, function, and disease relevance.Signal transduction and targeted therapy · 2023Review
- Differential toxicity and localization of arginine-richiScience · 2023Article
- Unraveling the impact of disrupted nucleocytoplasmic transport systems inFrontiers in cellular neuroscience · 2023Review
- Molecular basis of C9orf72 poly-PR interference with the β-karyopherin family of nuclear transport receptors.Scientific reports · 2022Article
- Random forest modelling demonstrates microglial and protein misfolding features to be key phenotypic markers in C9orf72-ALS.The Journal of pathology · 2022Article
- Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors.Biology · 2022Review
- Nuclear pore complexes - a doorway to neural injury in neurodegeneration.Nature reviews. Neurology · 2022Review
- Non-transport roles of nuclear import receptors: In need of the right balance.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
34 authors at 14 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration.
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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.