8R3Z

Cryo-EM structure of the Asgard archaeal Argonaute HrAgo1 bound to a guide RNA

Summary for 8R3Z

• Entry DOI: 10.2210/pdb8r3z/pdb
• EMDB information: 18878
• Descriptor: HrAgo1, RNA (5'-R(P*UP*GP*AP*GP*GP*U*(MG))-3'), MAGNESIUM ION (3 entities in total)
• Functional Keywords: argonaute, rna, rna binding protein
• Biological source: Candidatus Harpocratesius repetitus; More
• Total number of polymer chains: 2
• Total formula weight: 102206.21

Authors

Finocchio, G.,Swarts, D.,Jinek, M. (deposition date: 2023-11-10, release date: 2024-06-19, Last modification date: 2024-07-10)

Primary citation

Bastiaanssen, C.,Bobadilla Ugarte, P.,Kim, K.,Finocchio, G.,Feng, Y.,Anzelon, T.A.,Kostlbacher, S.,Tamarit, D.,Ettema, T.J.G.,Jinek, M.,MacRae, I.J.,Joo, C.,Swarts, D.C.,Wu, F.
RNA-guided RNA silencing by an Asgard archaeal Argonaute.
Nat Commun, 15:5499-5499, 2024

PubMed Abstract: Argonaute proteins are the central effectors of RNA-guided RNA silencing pathways in eukaryotes, playing crucial roles in gene repression and defense against viruses and transposons. Eukaryotic Argonautes are subdivided into two clades: AGOs generally facilitate miRNA- or siRNA-mediated silencing, while PIWIs generally facilitate piRNA-mediated silencing. It is currently unclear when and how Argonaute-based RNA silencing mechanisms arose and diverged during the emergence and early evolution of eukaryotes. Here, we show that in Asgard archaea, the closest prokaryotic relatives of eukaryotes, an evolutionary expansion of Argonaute proteins took place. In particular, a deep-branching PIWI protein (HrAgo1) encoded by the genome of the Lokiarchaeon 'Candidatus Harpocratesius repetitus' shares a common origin with eukaryotic PIWI proteins. Contrasting known prokaryotic Argonautes that use single-stranded DNA as guides and/or targets, HrAgo1 mediates RNA-guided RNA cleavage, and facilitates gene silencing when expressed in human cells and supplied with miRNA precursors. A cryo-EM structure of HrAgo1, combined with quantitative single-molecule experiments, reveals that the protein displays structural features and target-binding modes that are a mix of those of eukaryotic AGO and PIWI proteins. Thus, this deep-branching archaeal PIWI may have retained an ancestral molecular architecture that preceded the functional and mechanistic divergence of eukaryotic AGOs and PIWIs.

PubMed: 38951509
DOI: 10.1038/s41467-024-49452-1

Experimental method

ELECTRON MICROSCOPY (3.4 Å)