TY - JOUR
T1 - HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse
AU - Ichiyanagi, Tomoko
AU - Ichiyanagi, Kenji
AU - Ogawa, Ayako
AU - Kuramochi-Miyagawa, Satomi
AU - Nakano, Toru
AU - Chuma, Shinichiro
AU - Sasaki, Hiroyuki
AU - Udono, Heiichiro
N1 - Funding Information:
We thank Dr Alex Bortvin (Carnegie Institute) for supplying the anti-L1 antibody and Drs Takehisa Sakaguchi and Takashi Sado (Kyushu University) for technical advice.Ms Megumi Iwata is acknowledged for her technical assistance. We also thank Dr Akihiro Matsukawa and Mr Haruyuki Watanabe (Okayama University) for the use of the cryostat. Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [22501027 to H.U., 20062010 to H.S., 25503003 and 21200037 to K.I.]; Takeda Foundation (to K.I. and H.U.); Naito Foundation (to H.U.); Women Researchers'' Handin- Hand Program at Kyushu University (to T.I.). Funding for open access charge: The Takeda Foundation (to H.U.). Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2014.
PY - 2014/10/29
Y1 - 2014/10/29
N2 - 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 Hsp90a 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 Hsp90a 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 Hsp90a 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.
AB - 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 Hsp90a 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 Hsp90a 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 Hsp90a 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.
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U2 - 10.1093/nar/gku881
DO - 10.1093/nar/gku881
M3 - Article
C2 - 25262350
AN - SCOPUS:84925283463
SN - 0305-1048
VL - 42
SP - 11903
EP - 11911
JO - Nucleic acids research
JF - Nucleic acids research
IS - 19
ER -