Prokaryotic Argonautes - variations on the RNA interference theme

Abstract

The discovery of RNA interference (RNAi) has been a major scientific breakthrough. This RNA-guided RNA interference system plays a crucial role in a wide range of regulatory and defense mechanisms in eukaryotes. The key enzyme of the RNAi system is Argonaute (Ago), an endo-ribonuclease that uses a small RNA guide molecule to specifically target a complementary RNA transcript. Two functional classes of eukaryotic Ago have been described: catalytically active Ago that cleaves RNA targets complementary to its guide, and inactive Ago that uses its guide to bind target RNA to down-regulate translation efficiency. A recent comparative genomics study has revealed that Argonaute-like proteins are also encoded by prokaryotic genomes. Interestingly, there is a lot of variation among these prokaryotic Argonaute (pAgo) proteins with respect to domain architecture: some resemble the eukaryotic Ago (long pAgo) containing a complete or disrupted catalytic site, while others are truncated versions (short pAgo) that generally contain an incomplete catalytic site. Prokaryotic Agos with an incomplete catalytic site often co-occur with (predicted) nucleases. Based on this diversity, and on the fact that homologs of other RNAi-related protein components (such as Dicer nucleases) have never been identified in prokaryotes, it has been predicted that variations on the eukaryotic RNAi theme may occur in prokaryotes.

Keywords: Archaea; Argonaute; Bacteria; RNAi.

Figure 1. FIGURE 1: Prokaryotic variations of the eukaryotic RNAi theme.

Eukaryotic Argonautes acquire short RNA guides to target complementary RNA molecules, resulting in silencing of expression of the corresponding gene; in case the Argonautes possess an intact active site, this will result in nucleolytic cleavage of the target RNA. Two types of prokaryotic Argonautes have recently been characterized. The RsAgo acquires guides from plasmid-derived mRNA, that allow binding of the complementary DNA strand of a plasmid; as RsAgo is inactive (*), it requires an additional nucleolytic enzyme for target cleavage. On the contrary, the active TtAgo acquires small DNA guides (mainly from plasmids) that allow for binding and cleavage of plasmid DNA strands.