DNA silencing by prokaryotic Argonaute proteins adds a new layer of defense against invading nucleic acids.

Argonaute (Ago) proteins are encoded in all three domains of life and are responsible for the regulation of intracellular nucleic acid levels. Whereas some Ago variants are able to cleave target nucleic acids by their endonucleolytic activity, others only bind to their target nucleic acids while target cleavage is mediated by other effector proteins. Although all Ago proteins show a high degree of overall structural homology, the nature of the nucleic acid binding partners differs significantly. Recent structural and functional data have provided intriguing new insights into the mechanisms of archaeal and bacterial Ago variants demonstrating the mechanistic diversity within the prokaryotic Ago family with astonishing differences in nucleic acid selection and nuclease specificity. In this review, we provide an overview of the structural organisation of archaeal Ago variants and discuss the current understanding of their biological functions that differ significantly from their eukaryotic counterparts.