Tumour-Derived Extracellular Vesicles Containing dsRNA Induce Degradation of Ribosomal Protein mRNA in Platelets

Area of Science:

• Molecular Biology
• Immunology
• Cancer Research

Background:

• Extracellular vesicles (EVs) mediate intercellular communication, carrying cargoes like nucleic acids.
• Previous research focused on RNA sequences, neglecting RNA structure in EVs.
• Tumor microenvironment communication is crucial for cancer progression.

Purpose of the Study:

• Investigate the role of RNA structure in tumor-derived EVs.
• Elucidate the communication between colorectal cancer EVs and platelets.
• Identify mechanisms of tumor-immune modulation via EV-mediated pathways.

Main Methods:

• Analysis of RNA content in colorectal cancer cell-derived EVs.
• Investigating the activation of dsRNA-sensing pathways in recipient cells, particularly platelets.
• Studying the OAS-RNASEL ribonuclease cascade and RNASEL/ABCE1/PELO axis activation in platelets.
• Assessing the impact of EV dsRNA on platelet transcriptome and ribosomal protein mRNA decay.

Main Results:

• Colorectal cancer cell EVs are enriched with endogenous double-stranded RNA (dsRNA).
• Tumor-derived EV dsRNA activates platelet OAS-RNASEL and RNASEL/ABCE1/PELO pathways.
• Platelet ribosomal protein mRNA undergoes decay upon activation by EV dsRNA.
• A novel pathway of tumor-platelet communication mediated by EV dsRNA is identified.

Conclusions:

• Endogenous dsRNA in tumor EVs acts as a danger-associated molecular pattern (DAMP).
• Tumor EVs reprogram platelet transcriptomes via dsRNA, modulating tumor-immune interactions.
• This study uncovers a new dimension of tumor-immune modulation through EV-mediated RNA reprogramming.