@article{96adab73603748aaa8ec80a3a9bba474,
title = "Piwi Nuclear Localization and Its Regulatory Mechanism in Drosophila Ovarian Somatic Cells",
abstract = "In Drosophila ovarian somatic cells (OSCs), Piwi represses transposons transcriptionally to maintain genome integrity. Piwi nuclear localization requires the N terminus and PIWI-interacting RNA (piRNA) loading of Piwi. However, the underlying mechanism remains unknown. Here, we show that Importinα (Impα) plays a pivotal role in Piwi nuclear localization and that Piwi has a bipartite nuclear localization signal (NLS). Impα2 and Impα3 are highly expressed in OSCs, whereas Impα1 is the least expressed. Loss of Impα2 or Impα3 forces Piwi to be cytoplasmic, which is rectified by overexpression of any Impα members. Extension of Piwi-NLS with an additional Piwi-NLS leads Piwi to be imported to the nucleus in a piRNA-independent manner, whereas replacement of Piwi-NLS with SV40-NLS fails. Limited proteolysis analysis suggests that piRNA loading onto Piwi triggers conformational change, exposing the N terminus to the environment. These results suggest that Piwi autoregulates its nuclear localization by exposing the NLS to Impα upon piRNA loading. Piwi represses transposons transcriptionally to maintain genome integrity. Yashiro et al. show that Importinα plays a pivotal role in Piwi nuclear localization and that Piwi has a bipartite nuclear localization signal at the N terminus. Piwi autoregulates its nuclear localization by exposing the nuclear localization signal to Impα upon piRNA loading.",
keywords = "Drosophila, Importin, PIWI, nuclear import, nuclear localization signal, piRNA",
author = "Ryu Yashiro and Yukiko Murota and Nishida, {Kazumichi M.} and Haruna Yamashiro and Kaede Fujii and Asuka Ogai and Soichiro Yamanaka and Lumi Negishi and Haruhiko Siomi and Siomi, {Mikiko C.}",
note = "Funding Information: We thank H. Ohtani for anti-Gasz antibody, Y. Tsuchizawa for plasmid construction, T. Shima for technical advice, and M. Oka and Y. Yoneda for discussions about properties of Impα proteins. We also thank members of the Siomi laboratories at the University of Tokyo and Keio University School of Medicine for technical advice and intensive discussion. This work was supported by a Grant-in-Aid for Scientific Research (S) ( 17H06111 ) from MEXT to M.C.S. Y.M., K.M.N., S.Y., and H.S. were supported by a Grant-in-Aid for Young Scientist (B) ( 16K18488 ), a Grant-in-Aid for Scientific Research (C) ( 15K06948 ), a Grant-in-Aid for scientific research on innovative areas ( 26112513 ), and a Grant-in-Aid for Scientific Research (S) ( 25221003 ), respectively, from MEXT . Funding Information: We thank H. Ohtani for anti-Gasz antibody, Y. Tsuchizawa for plasmid construction, T. Shima for technical advice, and M. Oka and Y. Yoneda for discussions about properties of Impα proteins. We also thank members of the Siomi laboratories at the University of Tokyo and Keio University School of Medicine for technical advice and intensive discussion. This work was supported by a Grant-in-Aid for Scientific Research (S) (17H06111) from MEXT to M.C.S. Y.M., K.M.N., S.Y., and H.S. were supported by a Grant-in-Aid for Young Scientist (B) (16K18488), a Grant-in-Aid for Scientific Research (C) (15K06948), a Grant-in-Aid for scientific research on innovative areas (26112513), and a Grant-in-Aid for Scientific Research (S) (25221003), respectively, from MEXT. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = jun,
day = "19",
doi = "10.1016/j.celrep.2018.05.051",
language = "English",
volume = "23",
pages = "3647--3657",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}