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TitleA conserved PIWI silencing complex detects piRNA-target engagement.
Journal, issue, pagesMol Cell, Vol. 85, Issue 17, Page 3275-33287.e7, Year 2025
Publish dateSep 4, 2025
AuthorsDipayan De / Sucharita Sarkar / Luca F R Gebert / Timothy Wiryaman / Todd A Anzelon / Ian J MacRae /
PubMed AbstractIn 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 ...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.
External linksMol Cell / PubMed:40912244 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 4.2 Å
Structure data

49407

9nhb

EMDB-49407, PDB-9nhb:
Cryo-EM structure of SIWI-piRNA-target(25-nt)-GTSF1 complex
Method: EM (single particle) / Resolution: 3.7 Å

49408

9nhc

EMDB-49408, PDB-9nhc:
Cryo-EM structure of SIWI-piRNA-target(49-nt)-GTSF1-Maelstrom complex
Method: EM (single particle) / Resolution: 3.6 Å

49409

9nhd

EMDB-49409, PDB-9nhd:
Cryo-EM structure of SIWI-piRNA-target(49-nt)-GTSF1-Maelstrom complex (conformation 2)
Method: EM (single particle) / Resolution: 4.1 Å

49410

9nhe

EMDB-49410, PDB-9nhe:
Cryo-EM structure of SIWI-piRNA-target(49-nt)-Maelstrom complex
Method: EM (single particle) / Resolution: 4.2 Å

49422

9nhs

EMDB-49422, PDB-9nhs:
Cryo-EM structure of SIWI-piRNA-target(39-nt)-GTSF1-Maelstrom-Spindle-E complex
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • bombyx mori (domestic silkworm)
  • synthetic construct (others)
KeywordsRNA BINDING PROTEIN/RNA / SIWI / GTSF1 / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex / Maelstrom / Spindle-E

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