Cross-kingdom RNAi: a universal mechanism of inter-organismal communication with many unknowns

Cross-kingdom RNAi (ck-RNAi) is a biological process in which small RNA (sRNA) molecules are transferred between organisms belonging to different kingdoms to silence specific genes. Although numerous instances of reciprocal ck-RNAi have been documented in plants, demonstrating a modulation of the interaction between plants and their pathogens, pests, or symbiotic partners, the underlying molecular mechanisms remain largely elusive. In this review, we distinguish between naturally occurring and transgene-based cases of ck-RNAi, examine the diverse mechanisms governing the transfer of primary ck-RNAi signals from donor to recipient organisms, and explore the prerequisites for their amplification and systemic spread. Finally, we highlight key unresolved questions concerning the mechanistic basis of ck-RNAi and offer a perspective on its potential role in co-evolutionary dynamics.