Show Notes
Castellano M et al., Cell Genomics - This study shows that extracellular ribonucleases mask the bioactivity of naked extracellular RNA (exRNA). When RNases are inhibited or absent, naked exRNA is internalized, triggers endosomal and cytosolic RNA sensors, and can enable translation of delivered mRNAs. Key terms: extracellular RNA, ribonuclease, TLR13, gymnosis, mRNA translation.
Study Highlights:
Inhibition or absence of extracellular RNases reveals that naked exRNA is spontaneously internalized by diverse cell types and induces pro-inflammatory responses. Internalized exRNA activates endosomal Toll-like receptors (including mouse TLR13 for bacterial rRNA) and, after endosomal escape, cytosolic RIG-I–like receptors via MAVS. Stabilized naked mRNAs can be translated in recipient cells in an RNase-dependent manner. In vivo RNase inhibition amplifies systemic immune activation while RNase-poor compartments (e.g., peritoneal cavity) respond to naked exRNA without added inhibitor.
Conclusion:
Extracellular RNases are a key barrier that prevents immune sensing and functional uptake of naked exRNA; controlling RNase activity reveals that nonvesicular exRNAs can mediate intercellular signaling, activate endosomal and cytosolic RNA sensors, and serve as translatable templates in recipient cells.
QC:
This episode was checked against the original article PDF and publication metadata.
Scope: article metadata and core scientific claims from the narration, excluding analogies, intro/outro, and music.
Factual QC score: 10/10.
Metadata QC score: 10/10.
Supported core claims: 7.
Claims flagged for review: 0.
Metadata checks passed: 4.
Metadata issues found: 0.
QC result: Pass.
Music:
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Article title:
Ribonuclease activity undermines immune sensing of naked extracellular RNA
First author:
Castellano M
Journal:
Cell Genomics
DOI:
10.1016/j.xgen.2025.100874
Reference:
Castellano M, Blanco V, Li Calzi M, Costa B, Witwer K, Hill M, Cayota A, Segovia M, Tosar JP. Ribonuclease activity undermines immune sensing of naked extracellular RNA. Cell Genomics. 2025;5:100874. https://doi.org/10.1016/j.xgen.2025.100874
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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