ArticleCell genomics2025
Ribonuclease activity undermines immune sensing of naked extracellular RNA.
Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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Who cites it
7 citing papers in PubMed.
- Next-Generation Nanocarrier Platforms for RNA Vaccines: Advances in Formulation, Stability Engineering, and Translational Manufacturing Challenges.Pharmaceutics · 2026Review
- Stress-induced breakup: tRNA-derived small RNAs in biology.Trends in cell biology · 2026Review
- Extracellular Small RNAs in Human Milk: Molecular Profiles, Stability and Fragment-Specific Responses in Cell-Based Assays.Non-coding RNA · 2026Article
- Engineered MSC-exosomes as CRISPR-Cas9 delivery vectors for precision immunotherapy.Frontiers in bioengineering and biotechnology · 2026Review
- Serum RNASE1 as a biomarker for disease activity and lupus nephritis in systemic lupus erythematosus.Frontiers in immunology · 2026Article
- The role of calcium homeostasis dysregulation in allergic rhinitis.Frontiers in immunology · 2026Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell membranes are thought of as barriers to extracellular RNA (exRNA) uptake. While naked exRNAs can be spontaneously internalized by certain cells, functional cytosolic delivery has been rarely observed. Here, we show that extracellular ribonucleases (RNases)-primarily from cell culture supplements-have obscured the study of exRNA functionality. When ribonuclease inhibitor (RI) is added to cell cultures, naked exRNAs can trigger pro-inflammatory responses in dendritic cells and macrophages, largely via endosomal Toll-like receptors (TLRs). Moreover, naked exRNAs can escape endosomes, engaging cytosolic RNA sensors. In addition, naked extracellular mRNAs can be spontaneously internalized and translated by various cell types in an RI-dependent manner. In vivo, RI co-injection amplifies naked-RNA-induced activation of splenic lymphocytes and myeloid leukocytes. Furthermore, naked RNA is inherently pro-inflammatory in RNase-poor compartments like the peritoneal cavity. These findings demonstrate that naked RNA is bioactive without requiring vesicular encapsulation, making a case for nonvesicular-exRNA-mediated intercellular communication.
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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.