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 <i>de novo</i> RNA synthesis in apoptotic cells and metabolites. In this study, we show that apoptotic mesenchymal stem cells (MSCs) and their apoptotic vesicles (apoVs) synthesize <i>de novo</i> 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 <i>de novo</i> 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 <i>de novo</i> RNAs and identifies that apoptotic LINE-2 RNAs can regulate innate immunity to prevent virus infection.