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TitleStructure of the MIWI endoribonuclease bound to pachytene piRNAs from mouse testes.
Journal, issue, pagesCell Rep, Vol. 45, Issue 1, Page 116804, Year 2026
Publish dateJan 12, 2026
AuthorsNicole Raad / Carmen Fernandez-Rodriguez / Radha Raman Pandey / Inayathulla Mohammed / Emiko Uchikawa / Fabienne Burger / David Homolka / Ramesh S Pillai /
PubMed AbstractPIWI-interacting RNAs (piRNAs) guide PIWI endoribonucleases to destroy transposon transcripts, ensuring animal fertility. Here, we report the cryo-electron microscopy structure of the MIWI-pachytene ...PIWI-interacting RNAs (piRNAs) guide PIWI endoribonucleases to destroy transposon transcripts, ensuring animal fertility. Here, we report the cryo-electron microscopy structure of the MIWI-pachytene piRNA complex isolated from mouse testes. The piRNA is held via non-specific charge-based interactions with the RNA backbone and by specific recognition of the first nucleotide uridine by residues within the MID and PIWI domains. The first six nucleotides of the guide RNA take up the A-form conformation to facilitate pairing with the target. The RNA channel is wider than that observed in insect PIWI proteins, explaining the tolerance for piRNA seed:target mismatches. The PIWI endonuclease domain is in an inactive "un-plugged" state, with the loop containing a catalytic residue (E671) requiring structural re-orientation for activity. Furthermore, the PIWI domain reveals a conserved pre-formed pocket that may serve to accommodate a conserved tryptophan from the interacting factor GTSF1 to promote small RNA-guided endoribonuclease activity.
External linksCell Rep / PubMed:41528842
MethodsEM (single particle)
Resolution2.89 - 4.2 Å
Structure data

54428

9s0z

EMDB-54428, PDB-9s0z:
Cryo-EM structure of the endogeneous MIWI in complex with pachytene piRNA at 3A
Method: EM (single particle) / Resolution: 3.0 Å

54446

9s1e

EMDB-54446, PDB-9s1e:
Cryo-EM structure of the endogeneous MIWI in complex with pachytene piRNA at 2.8A
Method: EM (single particle) / Resolution: 2.89 Å

54907

9shp

EMDB-54907, PDB-9shp:
Cryo-EM structure of the endogeneous MIWI in complex with pachytene piRNA at 3.3A
Method: EM (single particle) / Resolution: 3.7 Å

54908

9shq

EMDB-54908, PDB-9shq:
Cryo-EM structure of the endogeneous MIWI in complex with pachytene piRNA at 4.2A
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • mus musculus (house mouse)
KeywordsRNA BINDING PROTEIN / MIWI / PIWIL1 / piRNA / slicer / pachytene piRNA

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