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TitleStructural basis for piRNA targeting.
Journal, issue, pagesNature, Vol. 597, Issue 7875, Page 285-289, Year 2021
Publish dateSep 1, 2021
AuthorsTodd A Anzelon / Saikat Chowdhury / Siobhan M Hughes / Yao Xiao / Gabriel C Lander / Ian J MacRae /
PubMed AbstractPIWI proteins use PIWI-interacting RNAs (piRNAs) to identify and silence transposable elements and thereby maintain genome integrity between metazoan generations. The targeting of transposable ...PIWI proteins use PIWI-interacting RNAs (piRNAs) to identify and silence transposable elements and thereby maintain genome integrity between metazoan generations. The targeting of transposable elements by PIWI has been compared to mRNA target recognition by Argonaute proteins, which use microRNA (miRNA) guides, but the extent to which piRNAs resemble miRNAs is not known. Here we present cryo-electron microscopy structures of a PIWI-piRNA complex from the sponge Ephydatia fluviatilis with and without target RNAs, and a biochemical analysis of target recognition. Mirroring Argonaute, PIWI identifies targets using the piRNA seed region. However, PIWI creates a much weaker seed so that stable target association requires further piRNA-target pairing, making piRNAs less promiscuous than miRNAs. Beyond the seed, the structure of PIWI facilitates piRNA-target pairing in a manner that is tolerant of mismatches, leading to long-lived PIWI-piRNA-target interactions that may accumulate on transposable-element transcripts. PIWI ensures targeting fidelity by physically blocking the propagation of piRNA-target interactions in the absence of faithful seed pairing, and by requiring an extended piRNA-target duplex to reach an endonucleolytically active conformation. PIWI proteins thereby minimize off-targeting cellular mRNAs while defending against evolving genomic threats.
External linksNature / PubMed:34471284 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 8.6 Å
Structure data

EMDB-23061, PDB-7kx7:
Cryo-EM structure of Ephydatia fluviatilis PiwiA-piRNA complex
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-23062:
Cryo-EM structure of EfPiwiA(MID/PIWI domains)-piRNA-long-target complex
Method: EM (single particle) / Resolution: 8.6 Å

EMDB-23063, PDB-7kx9:
Cryo-EM structure of Ephydatia fluviatilis PiwiA-piRNA-target complex
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • ephydatia fluviatilis (invertebrata)
  • synthetic construct (others)
KeywordsHYDROLASE / RNA BINDING PROTEIN/RNA / RNASEH / PROTEIN-RNA COMPLEX / RNA BINDING PROTEIN / PIRNA BINDING / PAZ PIWI DOMAIN PROTEIN / RNA BINDING PROTEIN-RNA complex

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