Oxford University Press Acta Medica Okayama 0305-1048 42 19 2014 HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse 11903 11911 EN Tomoko Ichiyanagi Kenji Ichiyanagi Ayako Ogawa Satomi Kuramochi-Miyagawa Toru Nakano Shinichiro Chuma Hiroyuki Sasaki Heiichiro Udono HSP90, found in all kingdoms of life, is a major chaperone protein regulating many client proteins. We demonstrated that HSP90α, one of two paralogs duplicated in vertebrates, plays an important role in the biogenesis of fetal PIWI-interacting RNAs (piRNA), which act against the transposon activities, in mouse male germ cells. The knockout mutation of Hsp90α resulted in a large reduction in the expression of primary and secondary piRNAs and mislocalization of MIWI2, a PIWI homolog. Whereas the mutation in Fkbp6 encoding a co-chaperone reduced piRNAs of 28–32 nucleotides in length, the Hsp90α mutation reduced piRNAs of 24–32 nucleotides, suggesting the presence of both FKBP6-dependent and -independent actions of HSP90α. Although DNA methylation and mRNA levels of L1 retrotransposon were largely unchanged in the Hsp90α mutant testes, the L1-encoded protein was increased, suggesting the presence of post-transcriptional regulation. This study revealed the specialized function of the HSP90α isofom in the piRNA biogenesis and repression of retrotransposons during the development of male germ cells in mammals. No potential conflict of interest relevant to this article was reported.