Elucidation of Elavl2 dependent translational mechanism in brain

• Project/Area Number: 16K07247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Niigata University
• Principal Investigator: Yano Masato 新潟大学, 医歯学系, 准教授 (20445414)
• Co-Investigator(Kenkyū-buntansha): 矢野 佳芳 (早川佳芳) 新潟大学, 医学部, 産学官連携研究員 (60397320)
• Project Period (FY): 2016-10-21 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: RNA結合蛋白質 / HITS-CLIP / 翻訳制御 / リボソームプロファイル / Ribosomeプロファイル

Outline of Final Research Achievements

We focused on neuron specific RNA-binding protein, Elavl2 which display a unique expression pattern among Elavl family proteins to reveal Elavl2-dependent translational regulatory program in living brain. We established an in vivo analysis strategy for translational mechanism by using comprehensive Elavl2-RNA interaction map analysis (HITS-CLIP method), in vivo ribosome profiling analysis and regular mRNA sequence analysis. In this study, we succeeded in identifying genes involved in neuronal cell and synaptic function as Elavl2 target genes in the developing brain.

Academic Significance and Societal Importance of the Research Achievements

本研究は、生きたマウス脳組織中の細胞内におけるメッセンジャーRNAから機能性蛋白質の生合成過程をスナップショットすることで、生体内制御解析システムを構築するものである。特にアジア人における統合失調症トップ候補因子としても知られる神経特異的RNA結合蛋白質Elavl2を対象とした本研究による分子基盤の包括的理解は、翻訳制御の破綻によって引き起こされる精神、神経疾患の原因、メカニズム、治療戦略への基礎となることが期待される。

Research Products

• [Journal Article] An RNA Switch of a Large Exon of Ninein Is Regulated by the Neural Stem Cell Specific-RNA Binding Protein, Qki5 (2019)
  • Author(s): Hayakawa-Yano Yoshika、Yano Masato
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 5 Pages: 1010-1010
  • DOI: 10.3390/ijms20051010
  • Peer Reviewed / Open Access
• [Journal Article] Elavl3 regulates neuronal polarity through the alternative splicing of an embryo-specific exon in AnkyrinG. (2018)
  • Author(s): Ogawa Y, Yamaguchi J, Yano M, Uchiyama Y, Okano HJ
  • Journal Title: Neurosci Res. Volume: - Pages: 13-20
  • DOI: 10.1016/j.neures.2018.03.008
  • Peer Reviewed
• [Journal Article] An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling (2017)
  • Author(s): Hayakawa-Yano Yoshika、Suyama Satoshi、Nogami Masahiro、Yugami Masato、Koya Ikuko、Furukawa Takako、Zhou Li、Abe Manabu、Sakimura Kenji、Takebayashi Hirohide、Nakanishi Atsushi、Okano Hideyuki、Yano Masato
  • Journal Title: Genes & Development Volume: 31 Issue: 18 Pages: 1910-1925
  • DOI: 10.1101/gad.300822.117
  • Peer Reviewed / Open Access
• [Journal Article] RNA regulation went wrong in neurodevelopmental disorders: The example of Msi/Elavl RNA binding proteins. (2016)
  • Author(s): Yano M, Hayakawa-Yano Y, Okano H
  • Journal Title: Int J Dev Neurosci. Volume: 印刷中 Issue: 1 Pages: 124-30
  • DOI: 10.1016/j.ijdevneu.2016.01.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Musashi mediates translational repression of the Drosophila hypoxia inducible factor. (2016)
  • Author(s): Bertolin AP, Katz MJ, Yano M, Pozzi B, Acevedo JM, Blanco-Obregon D, Gandara L, Sorianello E, Kanda H, Okano H, Srebrow A, Wappner P.
  • Journal Title: Nucleic Acids Research Volume: 19 Issue: 16 Pages: 7555-67
  • DOI: 10.1093/nar/gkw372
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of in vitro FUS-associated familial amyotrophic lateral sclerosis model using human induced pluripotent stem cells. (2016)
  • Author(s): Naoki Ichiyanagi, Koki Fujimori, Masato Yano, Chikako Ishihara-Fujisaki, Takefumi Sone, Tetsuya Akiyama, Yohei Okada, Wado Akamatsu, Takuya Matsumoto, Mitsuru Ishikawa, Yoshinori Nishimoto, Yasuharu Ishihara, Tetsushi Sakuma, Takashi Yamamoto, Hitomi Tsuiji, Naoki Suzuki, Hitoshi Warita, Masashi Aoki, Hideyuki Okano
  • Journal Title: Stem Cell Reports Volume: 6 Issue: 4 Pages: 496-510
  • DOI: 10.1016/j.stemcr.2016.02.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma. (2016)
  • Author(s): Fox RG, Lytle NK, Jaquish DV, Park FD, Ito T, Bajaj J, Koechlein CS, Zimdahl B, Yano M, Kopp JL, Kritzik M, Sicklick JK, Sander M, Grandgenett PM, Hollingsworth MA, Shibata S, Pizzo D, Valasek MA, Sasik R, Scadeng M, Okano H, Kim Y, MacLeod AR, Lowy AM, Reya T.
  • Journal Title: Nature Volume: 534(7607) Issue: 7607 Pages: 407-411
  • DOI: 10.1038/nature17988
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of induced pluripotent stem cells carrying 22q11.2 deletion (2016)
  • Author(s): Toyoshima M, Akamatsu W, Okada Y, Ohnishi T, Balan S, Hisano Y, Iwayama Y, Toyota T, Matsumoto T, Itasaka N, Sugiyama S, Tanaka M, Yano M, Dean B, Okano H, Yoshikawa T
  • Journal Title: Translational Psychiatry Volume: 6 Issue: 11 Pages: e934-e934
  • DOI: 10.1038/tp.2016.206
  • Peer Reviewed / Open Access
• [Journal Article] 幹細胞、癌における細胞運命決定因子Musashiの役割 (2016)
  • Author(s): 矢野真人, 岡野栄之
  • Journal Title: 日本臨床 Volume: 74巻増刊号10 Pages: 503-507
• [Journal Article] ノンコーディングRNA (2016)
  • Author(s): 矢野真人
  • Journal Title: 脳科学辞典 Volume: なし
  • DOI: 10.14931/bsd.6736
• [Presentation] 蛋白質-RNA相互作用マッピングは、新しいRNA制御モデルとRNA制御オリゴの同定を可能にする (2019)
  • Author(s): 矢野真人
  • Organizer: 第18回日本再生医療学会シンポジウム 「RNA技術と幹細胞研究の最前線」
  • Invited
• [Presentation] Qki5 HITS-CLIP provides new mechanisms of RNA regulatory loop (2019)
  • Author(s): Masato Yano and Yoshika Yano
  • Organizer: The 20th Takeda Science Foundation Symposium on Bioscience "RNA Neobiology" ポスター発表
• [Presentation] 中枢神経系の細胞アイデンティティーを創出する RNA 結合蛋白質の解析 (2018)
  • Author(s): 矢野真人
  • Organizer: 武田薬品工業SILエキスパートシンポジウム”RNA-Binding Proteins in Neuroscience
  • Invited
• [Presentation] Cell-type specific RNA-binding proteins in the developing central nervous system (2018)
  • Author(s): Yano M, Okano H, Sakimura K, Takebayashi H, Suyama S and Hayakawa-Yano Y
  • Organizer: 第41回日本神経科学大会シンポジウム "RNA制御から理解する神経発生と疾患"
  • Invited
• [Presentation] The Future of Neuroscience discussion (2018)
  • Author(s): Masato Yano
  • Organizer: バイオジェン創立40周年記念式典 パネルディスカッション
  • Invited
• [Presentation] An RNA-binding protein Qki5 regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling (2018)
  • Author(s): Hayakawa-Yano Y, Suyama S, Nogami M, Yugami M, Koya I, Furukawa T, Zhou L, Abe M, Sakimura K, Takebayashi H, Nakanishi A, *Okano H, and *Yano M
  • Organizer: 第41回日本神経科学大会 ポスター発表
• [Presentation] An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling (2018)
  • Author(s): Hayakawa-Yano Y, Suyama S, Nogami M, Yugami M, Koya I, Furukawa T, Zhou L, Abe M, Sakimura K, Takebayashi H, Nakanishi A, *Okano H, and *Yano M
  • Organizer: 第８回新潟大学脳研究所共同研究拠点国際シンポジウム ポスター発表
• [Presentation] An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling (2017)
  • Author(s): Hayakawa-Yano Yoshika、Suyama Satoshi、Nogami Masahiro、Yugami Masato、Koya Ikuko、Furukawa Takako、Zhou Li、Abe Manabu、 Sakimura Kenji、Takebayashi Hirohide、Nakanishi Atsushi、Okano Hideyuki、Yano Masato
  • Organizer: CSHL meeting "40Years of mRNA splicing from discovery to therapeutics（国際学会）
  • Int'l Joint Research
• [Presentation] Alternative splicing in neural stem cells (2016)
  • Author(s): 矢野真人, 矢野佳芳, 岡野栄之
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Invited
• [Remarks] サイエンティスト脳の臨界期
  • URL: https://ncrna.jp/blog/item/436-critical-period
• [Remarks] 新規の神経幹細胞制御因子としてQuaking5の機能を解明しました
  • URL: https://www.niigata-u.ac.jp/news/2017/36258/
• [Remarks] 《新規の神経幹細胞制御因子としてQuaking5の機能を解明》
  • URL: https://www.keio.ac.jp/ja/press-releases/2017/10/13/28-24759/
• [Remarks] unbiasedなストラテジー
  • URL: https://ncrna.jp/blog/item/346-unbiased