ArticleThe EMBO journal2021
Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Peptide-phosphorodiamidate morpholino oligomer therapy for dysferlinopathy induces pseudoexon skipping and restoration of functional protein.JCI insight · 2026Article
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Discovery of a Minimally Charged Cell-Penetrating Peptide.Biochemistry · 2026Article
- Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism.Brain communications · 2026Review
- The impact of chemical modifications of antisense oligonucleotides on CTX-M-15 β-lactamase target affinity and expression of ceftriaxone-resistantNAR molecular medicine · 2026Article
- Article
- In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific PET Probe.Bioconjugate chemistry · 2025Article
- Nucleic Acid Conjugates: Unlocking Therapeutic Potential.ACS bio & med chem Au · 2025Review
- The proline-rich antimicrobial peptide Api137 disrupts large ribosomal subunit assembly and induces misfolding.Nature communications · 2025Article
- Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications.Molecular biomedicine · 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
- CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides againstScience advances · 2023Article
- Nucleosomes in mammalian sperm: conveying paternal epigenetic inheritance or subject to reprogramming between generations?Current opinion in genetics & development · 2023Review
- Reduced C9orf72 expression exacerbates polyGR toxicity in patient iPSC-derived motor neurons and a Type I protein arginine methyltransferase inhibitor reduces that toxicity.Frontiers in cellular neuroscience · 2023Article
- Arg/Lys-containing IDRs are cryptic binding domains for ATP and nucleic acids that interplay to modulate LLPS.Communications biology · 2022Article
- HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS.Acta neuropathologica · 2022Article
- Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM.Nature communications · 2022Article
- Cell-penetrating peptides improve pharmacokinetics and pharmacodynamics of anticancer drugs.Tissue barriers · 2022Review
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- A Streamlined Data Analysis Pipeline for the Identification of Sites of Citrullination.Biochemistry · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to their capability to transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic lateral sclerosis (ALS) as a model of an arginine-rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA- and DNA-binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids, such as RNA transcription, translation, splicing and degradation, or DNA replication and repair, is impaired by the presence of the CPPs. Interestingly, the effects of (PR)n are fully mimicked by protamine, a small arginine-rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA- and DNA-binding factors from chromatin and mRNA accounts for the toxicity of arginine-rich CPPs, including those that have been recently associated with the onset of ALS.
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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.