Studies on the roles of small RNA in mice

2013 Fiscal Year Final Research Report

• Project Area: Functional machinery for non-coding RNAs
• Project/Area Number: 21115006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University (2013); The University of Tokyo (2009-2012)
• Principal Investigator: NAKAZAWA Takanobu 大阪大学, 薬学研究科(研究院), 特任准教授 (00447335)
• Co-Investigator(Kenkyū-buntansha): MIYAGAWA Satomi 大阪大学, 大学院医学系研究科, 特任講師 (90291153)
• Project Period (FY): 2009-07-23 – 2014-03-31
• Keywords: 小分子RNA / miRNA / piRNA / non-coding RNA / 中枢神経系 / 精巣 / 神経細胞 / 精子形成

Research Abstract

In this study, we showed the importance of small RNAs in brain and testis as described below. 1) We found that several miRNAs in the striatum are involved in cocaine addiction. 2) Using unbiased screening methods, we found that several miRNAs, such as miR-132, regulates neural morphogenesis. 3) To analyze the molecular function of MILI in piRNA biogenesis, we utilized germline stem (GS) cells, which are derived from testicular stem cells and possess a spermatogonial phenotype. We found that glycerol-3-phosphate acyltransferase 2 (GPAT2), a mitochondrial outer membrane protein for lysophosphatidic acid, bounds to MILI in GS cells. 4) We developed a novel artificial piRNA production system to reveal that the concomitant expression of sense and antisense RNA transcripts is necessary and sufficient for piRNA production and subsequent piRNA-dependent gene silencing.

Research Products

• [Journal Article] Retrograde Semaphorin Signaling Regulates Synapse Elimination in the Developing Mouse Brain (2014)
  • Author(s): Uesaka N, Uchigashima M, Mikuni T,Nakazawa T, Nakao H, Hirai H, Aiba A,Watanabe M, Kano M.
  • Journal Title: Science Volume: 344(PMID:24831527) Pages: 1020-1023
• [Journal Article] LMTK3 Deficiency Causes Pronounced Locomotor Hyperactivity and Impairs Endocytic Trafficking (2014)
  • Author(s): Inoue T, Hoshina N, Nakazawa T, Kiyama Y, Kobayashi S, Abe T, Yamamoto T, Manabe T, Yamamoto T.
  • Journal Title: J Neurosci Volume: 34(17) Pages: 5927-5937
  • DOI: 10.1523/JNEUROSCI.1621-13.2014
• [Journal Article] Analysis of DNA methylation in Mouse Testis (2014)
  • Author(s): Kuramochi-Miyagawa S, Kojima-Kita K, Shiromoto Y, Itou D, Koshima H, Nakano T
  • Journal Title: Methods in Mol. Biol Volume: 1093 Pages: 97-109
  • DOI: 10.1007/978-1-62703-694-8_8
• [Journal Article] Protocadherin 17 regulates presynaptic assembly in topographic corticobasal Ganglia circuits (2013)
  • Author(s): Hoshina N, Tanimura A, Yamasaki M, Inoue T, Fukabori R, Kuroda T, Yokoyama K, Tezuka T, Sagara H, Hirano S, Kiyonari H, Takada M, Kobayashi K, Watanabe M, Kano M, Nakazawa T, Yamamoto T
  • Journal Title: Neuron Volume: 78(5) Pages: 839-854
  • DOI: 10.1016/j.neuron.2013.03.031
• [Journal Article] The nuage mediates retrotransposon silencing in mouse primordial ovarian follicles (2013)
  • Author(s): Lim AK, Lorthongpanich C, Chew TG, Tan CW, Shue YT, Balu S, Gounko N, Kuramochi-Miyagawa S, Matzuk MM, Chuma S, Messerschmidt DM, Solter D, Knowles BB
  • Journal Title: Development Volume: 140(18) Pages: 3819-3825
  • DOI: 10.1242/dev.099184
• [Journal Article] Targeted gene silencing in mouse germ cells by insertion of a homologous DNA into a piRNA generating locus (2013)
  • Author(s): Yamamoto Y, Watanabe T, Hoki Y, Shirane K, Li Y, Ichiiyanagi K, Kuramochi-Miyagawa S, Toyoda A, Fujiyama A, Oginuma M, Suzuki H, Sado T, Nakano T, Sasaki H
  • Journal Title: Genome Res Volume: 23(2) Pages: 292-299
  • DOI: 10.1101/gr.137224.112
• [Journal Article] Metaplasticity gated through differential regulation of GluN2A versus GluN2B receptors by Src family kinases (2012)
  • Author(s): Yang K, Trepanier C, Sidhu B, Xie YF, Li H, Lei G, Salter MW, Orser BA, Nakazawa T, Yamamoto T, Jackson MF, Macdonald JF
  • Journal Title: EMBO J Volume: 31(4) Pages: 805-816
  • DOI: 10.1038/emboj.2011.453
• [Journal Article] NYAP : a phosphoprotein family that links PI3K to WAVE1 signalling in neurons (2011)
  • Author(s): Yokoyama K, Tezuka T, Kotani M, Nakazawa T, Hoshina N, Shimoda Y, Kakuta S, Sudo K, Watanabe K, Iwakura Y, Yamamoto T.
  • Journal Title: EMBO J Volume: 30(23) Pages: 4739-4754
  • DOI: 10.1038/emboj.2011.348
• [Journal Article] Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development (2011)
  • Author(s): Ichiyanagi K, Li Y, Watanabe T, Ichiyanagi T, Fukuda K, Kitayama J, Yamamoto Y, Kuramochi-Miyagawa S, Nakano T, Yabuta Y, Seki Y, Saitou M, Sasaki H
  • Journal Title: Genome Res Volume: 21 Pages: 2058-2066
  • DOI: 10.1101/gr.123679.111
• [Journal Article] Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis (2011)
  • Author(s): Tanaka T, Hosokawa M, Vagin VV, Reuter M, Hayashi E, Mochizuki AL, Kitamura K, Yamanaka H, Kondoh G, Okawa K, Kuramochi-Miyagawa S, Nakano T, Sachidanandam R, Hannon GJ, Pillai RS, Nakatsuji N, Chuma S.
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 10579-10584
  • DOI: 10.1073/pnas.1015447108.
• [Journal Article] Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus (2011)
  • Author(s): Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H
  • Journal Title: Science Volume: 332 Pages: 848-852
  • DOI: 10.1126/science.1203919
• [Journal Article] MITOPLD is a mitochondrial protein essential for nuage nuage formation and piRNA buigenesis in the mouse germline (2011)
  • Author(s): Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T, Noce T, Nakano T, Nakatsuji N, Lin H, Sasaki H
  • Journal Title: Dev Cell Volume: 23 Pages: 364-375
  • DOI: 10.1016/j.devcel.2011.01.005
• [Journal Article] MVH in piRNA Processing and Gene Silencing of Retrotransposons (2010)
  • Author(s): Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Takamatsu K, Chuma S, Kojima-Kita K, Shiromoto Y, Asada N, Toyoda A, Fujiyama A, Totoki Y, Shibata T, Kimura T, Nakatsuji N, Noce T, Sasaki H, Nakano T
  • Journal Title: Genes Dev Volume: 23 Pages: 887-892
  • DOI: 10.1101/gad.1902110
• [Journal Article] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour (2009)
  • Author(s): Taniguchi S, Nakazawa T, Tanimura A, Kiyama Y, Tezuka T, Watabe AM, Katayama N, Yokoyama K, Inoue T, Izumi-Nakaseko H, Kakuta S, Sudo K, Iwakura Y, Umemori H, Inoue T, Murphy NP, Hashimoto K, Kano M, Manabe T, Yamamoto T
  • Journal Title: EMBO J Volume: 28(23) Pages: 3717-3729
  • DOI: 10.1038/emboj.2009.300
• [Presentation] MVH ヘリカーゼ活性はLINE-1 レトロトランスポゾンの抑制に必須である (2013)
  • Author(s): 伊藤大介、宮川さとみ、仲野徹
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 20131203-06
• [Presentation] 神経細胞の形態形成と統合失調症 (2013)
  • Author(s): 中澤敬信
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館(京都府京都市)
  • Year and Date: 20130620-23
• [Presentation] Association between the p250GAP/TCGAP family of RhoGAP genes and schizophrenia (2012)
  • Author(s): 中澤敬信
  • Organizer: 第35回日本神経科学会大会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2012-09-19
• [Presentation] PAT2, a mitochondrial acyltransferase, in piRNA biogenesis in germline stem cells (2012)
  • Author(s): Shiromoto Y, Kuramochi-Miyagawa S, Daiba A, Chuma S, Nishimura K, Nakano T
  • Organizer: REGULATORY & NON-CODING RNAs in Cold Spring Habor Laboratory meeting
  • Place of Presentation: Cold Spring Habor Laboratory, New York, USA
  • Year and Date: 2012-08-30
• [Presentation] Production and function of piRNA in spermatogenesis (2011)
  • Author(s): Kuramochi-Miyagawa S
  • Organizer: アジアRNA 会議
  • Place of Presentation: 淡水福容ホテル 台湾
  • Year and Date: 2011-11-11
• [Presentation] Essential role of tyrosine phosphorylation of the NMDA receptor in mouse behavior (2011)
  • Author(s): Nakazawa T.
  • Organizer: ISN-ESN2011
  • Place of Presentation: Greece Megaron Athens International Conference Center, Greece
  • Year and Date: 2011-08-30
• [Presentation] piRNA : its production and possible functions (2010)
  • Author(s): Kuramochi-Miyagawa S
  • Organizer: 2010 SDB and JSDB Joint Meeting
  • Place of Presentation: Albuquerque, USA
  • Year and Date: 2010-08-05
• [Presentation] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behavior (2009)
  • Author(s): 中澤敬信
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2009-12-12
• [Presentation] small RNA とエピジェネティック制御 (2009)
  • Author(s): 宮川さとみ
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2009-10-22
• [Remarks]
  • URL: http://molpharm.umin.jp/
• [Remarks]
  • URL: http://www.fbs.osaka-u.ac.jp/labs/nakano/