From immunity to identity to exaptation: RNA-based self/non-self discrimination across cellular life

Distinguishing self from non-self is a universal imperative of life, where such discrimination at RNA level is both evolutionarily rational and urgently required to maintain homeostasis. Across kingdoms, organisms have evolved distinct yet convergent strategies to achieve this goal. Animals broadly employ A-to-I mRNA editing and other modifications as self-tags; plants and fungi mainly rely on RNA interference, spatial segregation, and m⁶A methylation; and prokaryotes utilize CRISPR-Cas immunity as a programmable analog of self-recognition. Despite their efficacy, these systems harbor intrinsic vulnerabilities that viruses might exploit through mimicry and modification theft, perpetuating a dynamic host-pathogen arms race. During evolution, these defense mechanisms might be exapted for new roles in hosts: A-to-I editing diversified proteomes, and m⁶A methylation became a global regulator of mRNA fate. Together, these observations reveal that mechanisms born from conflict might be repurposed to drive molecular innovation, linking self-recognition, adaptation, and the evolution of complexity.