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A conserved PIWI silencing complex detects piRNA-target engagement.

Dipayan De·Sucharita Sarkar·Luca F R Gebert·Timothy Wiryaman·Todd A Anzelon·Ian J MacRae
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Abstract

In animal germ cells, PIWI proteins use piRNAs to detect active selfish genetic elements. Base-pairing to a piRNA defines transposon recognition, but how this interaction triggers a defensive response remains unclear. Here, we identify a transposon recognition complex composed of the silkworm proteins Siwi, GTSF1, and Maelstrom. Biochemical and cryo-electron microscopy (cryo-EM) analyses show that extended piRNA-target pairing locks Siwi in a conformation that recruits GTSF1 and Maelstrom. Extended piRNA-target pairing is recognized by the N-terminal helix of Maelstrom and the first zinc finger of GTSF1, which act together to hold Siwi in an endonucleolytically active state. The resulting activated complex, termed Siwi∗, rapidly cleaves target RNAs and recruits the piRNA biogenesis factor Spindle-E. Structural predictions reveal related complexes in animals ranging from humans to sponges, indicating PIWI∗ assembly is a conserved transposon recognition mechanism employed broadly across the metazoan kingdom.

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AnimalsRNA, Small InterferingArgonaute ProteinsCryoelectron MicroscopyBombyxDNA Transposable ElementsInsect ProteinsProtein BindingModels, MolecularHumansPiwi-Interacting RNAGTSF1MaelstromPiwiSiwipiRNAsilencingtransposible elementtransposonJournal Article

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Dipayan De, Sucharita Sarkar, Luca F R Gebert, Timothy Wiryaman, Todd A Anzelon, Ian J MacRae. 2025-09-04. A conserved PIWI silencing complex detects piRNA-target engagement.. https://doi.org/10.1016/j.molcel.2025.08.010

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