Identification and functional analysis of the factor related to yki mRNA subcellular localization and translational repression

• Project/Area Number: 17K07385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Yoshida Hideki 京都工芸繊維大学, 応用生物学系, 准教授 (30570600)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ショウジョウバエ / yki / mRNA局在化 / yki mRNA / 翻訳抑制 / P-body / mRNA細胞内局在 / yorkie mRNA / P-bodies

Outline of Final Research Achievements

We biologically identified 13 proteins, including two aminoacyl tRNA synthetases (ARS), which are purified with the 3’ untranslated region of yki mRNA by using a mass spectrometer. Therefore, we investigated whether yki genetically interact with other tRNA synthetases. As a result, we found at least 14 ARSs were genetically interacting with yki and showed a loss of pigmentation or the ectopic melanization especially in the posterior region, which are not typical phenotypes derived from yki overexpression. Because we found that the amount of Yki protein in ARS knockdown cells was increased, we will investigate whether the amount of Yki protein in ARS knockdown flies is also increased.

Academic Significance and Societal Importance of the Research Achievements

yki遺伝子の哺乳類相同遺伝子はYAPであり、様々ながんで高発現するがん遺伝子である。YkiやYAPは、がん抑制経路Hippo経路を介して、リン酸化により抑制的に制御される。このリン酸化部位に変異をもつYkiやYAPの過剰発現は、がん化を誘導することから、リン酸化の制御の重要性が注目されてきた。しかし、一方で、がん患者のYAPのリン酸化部位に変異は見つかっておらず、またYAPタンパク質の高発現の原因も明らかになっていない。今回、我々は、ARSとykiが遺伝学的に相互作用すること、ARSノックダウンによりYkiタンパク質が増加することを見出し、がん化メカニズムの解明に迫る可能性を示した。

Research Products

• [Journal Article] Identification of CR43467 encoding a long non-coding RNA as a novel genetic interactant with dFIG4, a CMT-causing gene. (2020)
  • Author(s): Shimada, S., Muraoka, Y., Ibaraki, K., Takano-Shimizu-Kouno, T., Yoshida, H., and Yamaguchi, M.
  • Journal Title: Experimental Cell Research Volume: 386 Issue: 1 Pages: 111711-111711
  • DOI: 10.1016/j.yexcr.2019.111711
  • Peer Reviewed
• [Journal Article] Neuron-specific knockdown of Drosophila HADHB induces a shortened lifespan, deficient locomotive ability, abnormal motor neuron terminal morphology and learning disability. (2019)
  • Author(s): Li J, Suda K, Ueoka I, Tanaka R, Yoshida H, Okada Y, Okamoto Y, Hiramatsu Y, Takashima H, Yamaguchi M.
  • Journal Title: Exp. Cell Res. Volume: 379 Issue: 2 Pages: 150-158
  • DOI: 10.1016/j.yexcr.2019.03.040
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel roles of Drosophila FUS and Aub responsible for piRNA biogenesis in neuronal disorders. (2018)
  • Author(s): Wakisaka KT, Tanaka R, Hirashima T, Muraoka Y, Azuma Y, Yoshida H, Tokuda T, Asada S, Suda K, Ichiyanagi K, Ohno S, Itoh M, Yamaguchi M.
  • Journal Title: Brain Res. Volume: 18 Pages: 30646-30652
  • DOI: 10.1016/j.brainres.2018.12.028
  • Peer Reviewed / Open Access
• [Journal Article] Role of the smallish gene during Drosophila eye development. (2018)
  • Author(s): Tanaka R, Miyata S, Yamaguchi M, Yoshida H.
  • Journal Title: Gene Volume: 684 Pages: 10-19
  • DOI: 10.1016/j.gene.2018.10.056
  • Peer Reviewed / Open Access
• [Journal Article] Genetic screening of the genes interacting with Drosophila FIG4 identified a novel link between CMT-causing gene and long noncoding RNAs. (2018)
  • Author(s): Muraoka Y, Nakamura A, Tanaka R, Suda K, Azuma Y, Kushimura Y, Lo Piccolo L, Yoshida H, Mizuta I, Tokuda T, Mizuno T, Nakagawa M, Yamaguchi M.
  • Journal Title: Exp. Neurol. Volume: 310 Pages: 1-13
  • DOI: 10.1016/j.expneurol.2018.08.009
  • Peer Reviewed / Open Access
• [Journal Article] The ABD on the nascent polypeptide and PH domain are required for the precise Anillin localization in Drosophila syncytial blastoderm. (2018)
  • Author(s): Hirashima T, Tanaka R, Yamaguchi M, Yoshida H.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-018-31106-0
  • Peer Reviewed / Open Access
• [Journal Article] Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS. (2018)
  • Author(s): Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M.
  • Journal Title: Exp Cell Res. Volume: 371 Issue: 2 Pages: 311-321
  • DOI: 10.1016/j.yexcr.2018.08.001
  • Peer Reviewed / Open Access
• [Journal Article] NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene. (2018)
  • Author(s): Yamamoto I, Azuma Y, Kushimura Y, Yoshida H, Mizuta I, Mizuno T, Ueyama M, Nagai Y, Tokuda T, Yamaguchi M.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 11291-11291
  • DOI: 10.1038/s41598-018-29716-9
  • Peer Reviewed / Open Access
• [Journal Article] Novel Drosophila model for psychiatric disorders including autism spectrum disorder by targeting of ATP-binding cassette protein A. (2018)
  • Author(s): Ueoka, I., Kawashima, H., Konishi, A., Aoki, M., Tanaka, R., Yoshida, H., Maeda, T., Ozaki, M. and Yamaguchi, M.
  • Journal Title: Experimental Neurology Volume: 300 Pages: 51-59
  • DOI: 10.1016/j.expneurol.2017.10.027
  • Peer Reviewed
• [Journal Article] Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes. (2018)
  • Author(s): Suong, D. N. A., Shimaji, K., Pyo, J.-H., Park, J.-S., Yoshida, H., Yoo, M. and Yamaguchi, M.
  • Journal Title: Cellular Signalling Volume: 42 Pages: 194-210
  • DOI: 10.1016/j.cellsig.2017.10.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A new Drosophila model of Ubiquilin knockdown shows the effect of impaired proteostasis on locomotive and learning abilities. (2018)
  • Author(s): Jantrapirom S, Lo Piccolo L, Yoshida H, Yamaguchi M.
  • Journal Title: Exp Cell Res. Volume: 362 Issue: 2 Pages: 4611-471
  • DOI: 10.1016/j.yexcr.2017.12.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel Drosophila model for mitochondrial diseases by targeting of a solute carrier protein SLC25A46. (2018)
  • Author(s): Suda, K., Ueoka, I., Azuma, Y., Muraoka, Y., Yoshida, H. and Yamaguchi, M.
  • Journal Title: Brain Research Volume: 1689 Pages: 30-44
  • DOI: 10.1016/j.brainres.2018.03.028
  • Peer Reviewed / Open Access
• [Journal Article] The Drosophila DOCK family protein Sponge is required for development of the air sac primodium. (2017)
  • Author(s): Kazushige Morishita, Dang Ngoc Anh Suong, Hideki Yoshida and Masamitsu Yamaguchi.
  • Journal Title: Exp. Cell Res. Volume: 17 Issue: 2 Pages: 30165-30169
  • DOI: 10.1016/j.yexcr.2017.03.044
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neuron-specific knockdown of the Drosophila fat induces reduction of life span, deficient locomotive ability, shortening of motoneuron terminal branches and defects in axonal targeting. (2017)
  • Author(s): Nakamura A, Tanaka R, Morishita K, Yoshida H, Higuchi Y, Takashima H, Yamaguchi M.
  • Journal Title: Genes Cells Volume: 22 Issue: 7 Pages: 662-669
  • DOI: 10.1111/gtc.12500
  • Peer Reviewed
• [Journal Article] <i>Drosophila</i> DOCK Family Protein Zizimin Involves in Pigment Cell Differentiation in Pupal Retinae (2017)
  • Author(s): Ozasa F, Morishita K, Dang NAS, Miyata S, Yoshida H, Yamaguchi M.
  • Journal Title: Cell Structure and Function Volume: 42 Issue: 2 Pages: 117-129
  • DOI: 10.1247/csf.17014
  • NAID: 130006854168
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a. (2017)
  • Author(s): An PNT, Shimaji K, Tanaka R, Yoshida H, Kimura H, Fukusaki E, Yamaguchi M.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 1-14
  • DOI: 10.1038/s41598-017-07566-1
  • Peer Reviewed / Open Access
• [Journal Article] Histone methyltransferase G9a is a key regulator of the starvation-induced behaviors in Drosophila melanogaster. (2017)
  • Author(s): Shimaji, K., Tanaka, R., Maeda, T., Ozaki, M., Yoshida, H., Ohkawa, Y., Sato, T., Suyama, M. and Yamaguchi, M.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 14763-14763
  • DOI: 10.1038/s41598-017-15344-2
  • NAID: 120006368029
  • Peer Reviewed / Open Access
• [Presentation] Post-transcriptional regulation of yorkie proto-oncogene through its own non-coding region (2019)
  • Author(s): 吉田英樹
  • Organizer: International Conference of the Genetics Society of Korea 2019
  • Int'l Joint Research / Invited
• [Presentation] dia mRNAのsyncytial blastodermにおける局在メカニズム解析 (2019)
  • Author(s): 岩手楓
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] DCP2がykiの遺伝子発現を制御する (2019)
  • Author(s): 出口佳一
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] POST-TRANSCRIPTIONAL REGULATION OF YORKIE PROTO-ONCOGENE THROUGH ITS OWN NON-CODING REGION (2019)
  • Author(s): 吉田英樹
  • Organizer: The second JAPAN-ASEAN seminar
  • Int'l Joint Research
• [Presentation] Regulation of yorkie gene expression through its own non-coding region (2018)
  • Author(s): Hideki Yoshida, Takanari Umegawachi, Hiromu Koshida, Momoko Yamada, Kazuma Usui, Tetsuya Sato, Mikita Suyama, Yasuyuki Ohkawa, Krause M. Henry, Masamitsu Yamaguchi.
  • Organizer: 第70回日本細胞生物学会／第51回日本発生生物学会合同大会
• [Presentation] Novel post-transcriptional regulations of yorkie gene expression (2018)
  • Author(s): Hideki Yoshida, Takanari Umegawachi, Hiromu Koshida, Momoko Yamada, Kazuma Usui, Tetsuya Sato, Mikita Suyama, Yasuyuki Ohkawa, Krause M. Henry, Masamitsu Yamaguchi.
  • Organizer: The 13th Japanese Drosophila Research Conference
• [Presentation] ショウジョウバエ初期胚におけるanillin mRNAの局在に対する申請鎖の役割 (2018)
  • Author(s): 平島智貴、田中領、山口政光、吉田英樹
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] ALS原因遺伝子FUSショウジョウバエモデルの表現型を抑圧する新規エピジェネティック制御因子の同定 (2018)
  • Author(s): 大森健太郎、浅田賢志、吉田英樹、山口政光
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] ショウジョウバエCMT原因遺伝子dFIG4と遺伝学的に相互作用する遺伝子の同定 (2018)
  • Author(s): 村岡夕香、中村綾、田中領、須田晃治郎、東裕美子、櫛村由紀恵、Luca Lo Piccolo、吉田英樹、水田依久子、徳田隆彦、水野敏樹、山口政光
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] パーキンソン業（PD）新規原因遺伝子のショウジョウバエを用いた解析 (2018)
  • Author(s): 清水丈、吉田英樹、山口政光
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] エピジェネティック制御に基づく新規発症機構への挑戦 -ショウジョウバエモデルを用いたミトコンドリア病原因遺伝子SLC25A46の機能解析- (2018)
  • Author(s): 須田晃治郎、吉田英樹、山口政光
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] ショウジョウバエモデルを用いたヒト希少神経難病CMT原因遺伝子FIG4と遺伝学的に相互作用する遺伝子の同定 (2018)
  • Author(s): 島田咲、村岡夕香、茨木公英、吉田英樹、高野敏行、山口政光
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] AVCAファミリー遺伝子を標的としたショウジョウバエの新規自閉症モデルの解析 (2018)
  • Author(s): 上岡伊吹、吉田英樹、山口政光
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] Subcellular localization and functional analyses of Drosophila SLC25A46, mitochondrial diseases causing gene. (2018)
  • Author(s): Kojiro Suda, Hideki Yoshida, Masamitsu Yamaguchi
  • Organizer: 第70回日本細胞生物学会／第51回日本発生生物学会合同大会
• [Presentation] Drosophila Ubiquilin depletion reveals the impact of proteostasis impairment on locomotive and learning abilities. (2018)
  • Author(s): Salinee Jantrapirom Luca Lo Piccolo, Hideki Yoshida, Masamitsu Yamaguchi
  • Organizer: 第70回日本細胞生物学会／第51回日本発生生物学会合同大会
• [Presentation] Knockdown of the ASD-caousing gene dABCA in Drosophila pan-neuron affects behavior. (2018)
  • Author(s): Ibuki Ueoka, Hideki Yoshida, Masamitsu Yamaguchi
  • Organizer: The 13th Japanese Drosophila Research Conference
• [Presentation] The translational-dependent anillin mRNA localization in drosophila early embryo. (2018)
  • Author(s): Tomoki Hirashima, Ryo Tanaka, Masamitsu Yamaguchi, Hideki Yoshida
  • Organizer: The 13th Japanese Drosophila Research Conference
• [Presentation] The translation-dependent scraps mRNA localization in Drosophila early embryo (2017)
  • Author(s): 平島智貴
  • Organizer: EMBO Conference on RNA Localization and Local Translation
  • Int'l Joint Research
• [Presentation] ショウジョウバエ初期胚pseudo-cleavage furrow に局在化するmRNA の局在 化機構 (2017)
  • Author(s): 田中領
  • Organizer: 第69回日本細胞生物学会
• [Presentation] The subcellular localization of yorkie mRNA regulates its functional expression (2017)
  • Author(s): 吉田英樹
  • Organizer: EMBO Conference on RNA Localization and Local Translation
  • Int'l Joint Research
• [Presentation] ショウジョウバエ初期胚における anillin mRNA の翻訳依存的な局在機構の解析 (2017)
  • Author(s): 平島智貴
  • Organizer: RNAフロンティアミーティング2017
• [Presentation] 飢餓ストレスに応答するエピジェネティック制御因子の研究 (2017)
  • Author(s): 冨田早紀
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] がん遺伝子yki mRNAの細胞内局在を制御する因子の同定 (2017)
  • Author(s): 坂本優一
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ABCファミリー遺伝子を標的としたショウジョウバエの新規自閉症モデルの確立 (2017)
  • Author(s): 上岡伊吹
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] SLC25A46遺伝子を標的とした人希少神経版病Charcot-Marie-Tooth病の新規ショウジョウバエモデルの開発 (2017)
  • Author(s): 須田晃治郎
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ショウジョウバエ初期杯におけるscraps mRNAの翻訳依存的な局在化機構の解析 (2017)
  • Author(s): 平島智貴
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ALS原因遺伝子FUSのショウジョウバエホモログCabezaと遺伝学的相互作用するエピジェネティック制御因子の同定 (2017)
  • Author(s): 浅田賢志
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ショウジョウバエCOA7の神経特異的ノックダウンは運動能力の低下と神経筋接合部のシナプス長の短縮を誘導する (2017)
  • Author(s): 奥主隆太
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ショウジョウバエCMT原因遺伝子dFIG4の新規遺伝学的相互作用因子としての長鎖非コードRNA,CR18854の同定 (2017)
  • Author(s): 村岡夕香
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] ショウジョウバエモデルを用いたパーキンソン病（PD）原因候補遺伝子の解析 (2017)
  • Author(s): 清水丈
  • Organizer: 2017年度 生命科学系学会合同年次大会