Ribonuclease activity undermines immune sensing of naked extracellular RNA
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View abstract on PubMed
Summary
This summary is machine-generated.Extracellular RNAs (exRNAs) are functional without vesicles. Ribonuclease inhibitors reveal naked RNA triggers immune responses and intercellular communication, challenging previous barriers to exRNA research.
Area Of Science
- Molecular Biology
- Immunology
- Cell Biology
Background
- Cell membranes traditionally viewed as barriers to extracellular RNA (exRNA) uptake.
- Functional cytosolic delivery of naked exRNAs has been rarely observed, hindering understanding of their roles.
- Extracellular ribonucleases (RNases) in supplements may have obscured the study of exRNA functionality.
Purpose Of The Study
- To investigate the bioactivity and cellular uptake of naked exRNAs.
- To determine the role of ribonucleases in masking exRNA function.
- To explore the potential for nonvesicular intercellular communication mediated by naked exRNA.
Main Methods
- Utilized ribonuclease inhibitor (RI) in cell cultures to block RNase activity.
- Assessed pro-inflammatory responses in dendritic cells and macrophages via Toll-like receptors (TLRs).
- Investigated endosomal escape and cytosolic RNA sensor engagement.
- Examined internalization and translation of extracellular mRNAs.
- Evaluated in vivo effects of RI co-injection on immune cell activation.
- Tested naked RNA bioactivity in RNase-poor environments.
Main Results
- Naked exRNAs trigger pro-inflammatory responses in immune cells via TLRs when RNases are inhibited.
- Naked exRNAs can escape endosomes and activate cytosolic RNA sensors.
- Extracellular mRNAs are internalized and translated by cells in an RI-dependent manner.
- RI co-injection amplifies naked RNA-induced immune cell activation in vivo.
- Naked RNA demonstrates inherent pro-inflammatory properties in RNase-poor conditions.
Conclusions
- Extracellular ribonucleases obscure the functional potential of naked exRNAs.
- Naked RNAs are bioactive and can mediate intercellular communication without vesicular encapsulation.
- These findings support a model of nonvesicular exRNA-mediated communication.
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