Small RNAs guard CRISPR-Cas The microbial adaptive immunity system CRISPR-Cas benefits microbes by warding off genetic invaders, but it also inflicts a fitness cost because of occasional autoimmune reactions, rendering CRISPR loci evolutionarily unstable. Li et al. identified previously unnoticed toxin-antitoxin RNA pairs embedded within diverse CRISPR-Cas loci. The antitoxin RNA mimics a CRISPR RNA and repurposes the CRISPR immunity effector to transcriptionally repress a toxin RNA that would otherwise arrest cell growth by sequestering a rare transfer RNA. These small RNAs thus form a symbiosis with CRISPR, rendering CRISPR addictive to the host despite its fitness cost. These findings reveal how CRISPR-Cas can operate as a selfish genetic element. Science , this issue p. eabe5601