Apoptotic metabolites synthesize and inherit unique de novo L2a/L2b RNAs to prevent virus infection.

Apoptosis is indispensable for a variety of physio-pathological processes. RNA is one of essential macromolecules for life. Extensive RNA decay is a characteristic feature of apoptosis. However, it is unknown whether there is de novo RNA synthesis in apoptotic cells and metabolites. In this study, we show that apoptotic mesenchymal stem cells (MSCs) and their apoptotic vesicles (apoVs) synthesize de novo RNAs. Nascent RNA-seq showed apoptotic MSCs and apoVs produced numerous nascent RNAs that were different from those in living MSCs, including protein-coding and non-coding RNAs. Mechanistically, apoptotic de novo RNA synthesis was related to the caspase-3/Sp1/RNA polymerase axis. Additionally, we found the LINE-2a (L2a) and LINE-2b (L2b) RNAs were specifically transcribed in apoptotic MSCs and transferred into apoVs to prevent virus infection. Altogether, this study reveals a previously unknown phenomenon that apoptotic cells synthesize various de novo RNAs and identifies that apoptotic LINE-2 RNAs can regulate innate immunity to prevent virus infection.