Short and Sweet – on short prokaryotic Argonautes

Summary

Argonaute proteins (Agos) can be found in all living organisms. They bind small nucleic acids (guides) to target complementary nucleic acids (targets). In prokaryotes, Agos are involved in immunity against invading nucleic acids. This thesis describes the functions and mechanisms of short prokaryotic Agos (short pAgos), with a focus on short pAgos that are associated with a TIR domain, or SPARTA systems. We show that SPARTA binding to a guide and complementary target induces conformational changes that lead to SPARTA oligomerization and activation of the TIR domain to degrade the essential metabolite NAD+. In the cell, SPARTA collects guides that target invading nucleic acids, which leads to SPARTA activation and consequentially cell death. In this way, SPARTA removes infected cells from the population. We also review the existing literature about short pAgos from other clades, and show some preliminary data about divergent SPARTA systems and other uncharacterized short pAgos.