CRISPR-Cas regulates expression of embedded anti-phage defence systems.

Type I CRISPR-Cas loci embed and transcriptionally control diverse innate defence systems, a regulatory paradigm named CRISIS. Small non-canonical crRNA-like RNAs guide the I-C Cascade effector to promoters of immune cassettes, keeping basal expression sufficient for antiviral activity while preventing fitness costs such as growth impairment and exclusion of beneficial plasmids. When CRISPR-Cas is compromised by mutation or anti-CRISPR proteins, transcription of the embedded defences surges, raising innate immunity at the expense of host fitness. This casts CRISPR-Cas as a supervisor of a layered prokaryotic defence network, an 'immunity guard' strategy.