ArticleThe Journal of cell biology2021
Phase separation and toxicity of C9orf72 poly(PR) depends on alternate distribution of arginine.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Two dipeptide repeat proteins are produced from mammalian telomeric RNA previously thought to be a long non-coding RNA.RNA biology · 2026Review
- Protometabolically Generated NADH Mediates Material Properties of Aqueous Dispersions to Coacervate Microdroplets.Biomacromolecules · 2026Article
- Nucleophosmin 1 proteins as potential therapeutic targets in non-communicable chronic inflammatory diseases: a review of pathophysiological mechanisms.Frontiers in cell and developmental biology · 2026Review
- FRET-based biosensor moxCRONOS enables quantitative monitoring of macromolecular crowding in organelles and protein aggregates.Journal of biochemistry · 2025Article
- Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.Nature communications · 2025Article
- Understanding Biases in Liquid-Liquid Phase Separation: Investigating Amino Acid Enrichments in Phase-Separating Proteins toward Peptide Design.Biomacromolecules · 2025Article
- Smart coacervate microdroplets: biomimetic design, material innovations, and emerging applications in biomacromolecule delivery.Bioactive materials · 2025Review
- Article
- Coacervate-Based Delivery Systems: Bridging Fundamentals and Applications.ACS applied materials & interfaces · 2025Review
- Graphene Biosensor Differentiating Sensitive Interactions between Ribonucleic Acid and Dipeptide Repeats in Liquid-Liquid Phase Separation.ACS applied materials & interfaces · 2025Article
- Probing the Limits of Reactant Concentration and Volume in Primitive Polyphenyllactate Synthesis and Microdroplet Assembly Processes.ACS bio & med chem Au · 2025Article
- Neurological Diseases can be Regulated by Phase Separation.Reviews of physiology, biochemistry and pharmacology · 2025Review
- Interaction-Dependent Secondary Structure of Peptides in Biomolecular Condensates.Journal of the American Chemical Society · 2024Article
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- Cell-Penetrating and Enzyme-Responsive Peptides for Targeted Cancer Therapy: Role of Arginine Residue Length on Cell Penetration and In Vivo Systemic Toxicity.ACS applied materials & interfaces · 2024Article
- Article
- Differential toxicity and localization of arginine-richiScience · 2023Article
- Mammalian telomeric RNA (TERRA) can be translated to produce valine-arginine and glycine-leucine dipeptide repeat proteins.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neuroimmune dysfunction in frontotemporal dementia: Insights from progranulin and C9orf72 deficiency.Current opinion in neurobiology · 2022Review
- Phase separation of low-complexity domains in cellular function and disease.Experimental & molecular medicine · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arg (R)-rich dipeptide repeat proteins (DPRs; poly(PR): Pro-Arg and poly(GR): Gly-Arg), encoded by a hexanucleotide expansion in the C9ORF72 gene, induce neurodegeneration in amyotrophic lateral sclerosis (ALS). Although R-rich DPRs undergo liquid-liquid phase separation (LLPS), which affects multiple biological processes, mechanisms underlying LLPS of DPRs remain elusive. Here, using in silico, in vitro, and in cellulo methods, we determined that the distribution of charged Arg residues regulates the complex coacervation with anionic peptides and nucleic acids. Proteomic analyses revealed that alternate Arg distribution in poly(PR) facilitates entrapment of proteins with acidic motifs via LLPS. Transcription, translation, and diffusion of nucleolar nucleophosmin (NPM1) were impaired by poly(PR) with an alternate charge distribution but not by poly(PR) variants with a consecutive charge distribution. We propose that the pathogenicity of R-rich DPRs is mediated by disturbance of proteins through entrapment in the phase-separated droplets via sequence-controlled multivalent protein-protein interactions.
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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.