A Role for Fkbp6 and the Chaperone Machinery in piRNA Amplification and Transposon Silencing

Jordi Xiol, Elisa Cora, Rubina Koglgruber, Shinichiro Chuma, Sailakshmi Subramanian, Mihoko Hosokawa, Michael Reuter, Zhaolin Yang, Philipp Berninger, Andres Palencia, Vladimir Benes, Josef Penninger, Ravi Sachidanandam, Ramesh S. Pillai

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Epigenetic silencing of transposons by Piwi-interacting RNAs (piRNAs) constitutes an RNA-based genome defense mechanism. Piwi endonuclease action amplifies the piRNA pool by generating new piRNAs from target transcripts by a poorly understood mechanism. Here, we identified mouse Fkbp6 as a factor in this biogenesis pathway delivering piRNAs to the Piwi protein Miwi2. Mice lacking Fkbp6 derepress LINE1 (L1) retrotransposon and display reduced DNA methylation due to deficient nuclear accumulation of Miwi2. Like other cochaperones, Fkbp6 associates with the molecular chaperone Hsp90 via its tetratricopeptide repeat (TPR) domain. Inhibition of the ATP-dependent Hsp90 activity in an insect cell culture model results in the accumulation of short antisense RNAs in Piwi complexes. We identify these to be byproducts of piRNA amplification that accumulate only in nuage-localized Piwi proteins. We propose that the chaperone machinery normally ejects these inhibitory RNAs, allowing turnover of Piwi complexes for their continued participation in piRNA amplification.

Original languageEnglish
Pages (from-to)970-979
Number of pages10
JournalMolecular Cell
Volume47
Issue number6
DOIs
StatePublished - 28 Sep 2012

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