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Nucleic Acids Res. 2014 Oct 29;42(19):11903-11. doi: 10.1093/nar/gku881. Epub 2014 Sep 27.

HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse.

Author information

1
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
2
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
3
Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan CREST, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
4
Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
5
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan udono@cc.okayama-u.ac.jp.

Abstract

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.

PMID:
25262350
PMCID:
PMC4231750
DOI:
10.1093/nar/gku881
[Indexed for MEDLINE]
Free PMC Article

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