The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-biases of piRNAs

Elisa Cora, Radha R. Pandey, Jordi Xiol, Josh Taylor, Ravi Sachidanandam, Andrew A. McCarthy, Ramesh S. Pillai

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Piwi-interacting RNAs (piRNAs) guide Piwi Argonautes to suppress transposon activity in animal gonads. Known piRNA populations are extremely complex, with millions of individual sequences present in a single organism. Despite this complexity, specific Piwi proteins incorporate piRNAs with distinct nucleotide- and transposon strand-biases (antisense or sense) of unknown origin. Here, we examined the contribution of structural domains in Piwi proteins toward defining these biases. We report the first crystal structure of the MID domain from a Piwi Argonaute and use docking experiments to show its ability to specify recognition of 5′ uridine (1U-bias) of piRNAs. Mutational analyses reveal the importance of 5′ end-recognition within the MID domain for piRNA biogenesis in vivo. Finally, domain-swapping experiments uncover an unexpected role for the MID-PIWI module of a Piwi protein in dictating the transposon strand-orientation of its bound piRNAs. Our work identifies structural features that allow distinguishing individual Piwi members during piRNA biogenesis.

Original languageEnglish
Pages (from-to)773-781
Number of pages9
Issue number6
StatePublished - Jun 2014


  • MID
  • PiRNA
  • Piwi
  • Strand-bias
  • U1-bias


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