Elucidation of the molecular mechanism for inhibition of let-7 miRNA function by RNA-binding protein Musashi1

• Project/Area Number: 21700413
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: IMAI Takao Keio University, 医学部, 助教 (10383712)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: RNA結合蛋白質 / 神経幹細胞 / miRNA / 翻訳 / let-7 / Musashi / 神経細胞 / RNA / 翻訳制御 / 神経系

Research Abstract

Musashi1 is an RNA-binding protein, which is expressed in neural stem/progenitor cells. I revealed following new findings. (1) Musashi1 directly bound to let-7 micro RNAs with sequence-specific manner. (2)Musashi1 inhibited the translational repression of let-7 down-stream target gene thorough the let-7. (3) There was the molecular aspect that Ago2 and Musashi1 exist in the same protein complex. (4)Musashi1 promoted the protein degradation of PAZ domain. The inhibition of let-7 function by Musashi1 is possibly due to the Musashi1-induced PAZ degradation.

Research Products

• [Journal Article] Identification of a Novel Intronic Enhancer Responsible for the Transcriptional Regulation of Musashil in Neural Stem/Progenitor Cells. (2011)
  • Author(s): Kawase S, Imai T, Miyauchi-Hara C, Yaguchi K, Nishimoto Y, Fukami SI, Matsuzaki Y, Miyawaki A, Itohara S, Okano H
  • Journal Title: Molecular Brain 4(1)[Epub ahead of print] Pages: 14-14
  • Peer Reviewed
• [Journal Article] Musashi 1 cooperates in abnormal cell LINeage protein 28 (Lin28)-mediated Let-7 family microRNA biogenesis in early neural differentiation. (2011)
  • Author(s): Kawahara H, Okada Y, Imai T, Iwanami A, Mischel PS, Okano H.
  • Journal Title: J Biol Chem. 286 Pages: 16121-16130
  • Peer Reviewed
• [Journal Article] Identification of a Novel Intronic Enhancer Responsible for the Transcriptional Regulation of Musashil in Neural Stem/Progenitor Cells. (2011)
  • Author(s): Kawase S, Imai T, Miyauchi-Hara C, Yaguchi K, Nishimoto Y, Fukami SI, Matsuzaki Y, Miyawaki A, Itohara S, Okano H
  • Journal Title: Molecular Brain Volume: 4(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Musashi 1 cooperates in abnormal cell LINeage protein 28 (Lin28)-mediated Let-7 family microRNA biogenesis in early neural differentiation. (2011)
  • Author(s): Kawahara H, Okada Y, Imai T, Iwanami A, Mischel PS, Okano H.
  • Journal Title: Journal of Biological Chemistry Volume: 286(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Neural RNA-binding protein Musashil controls midline crossing of precerebellar neurons through posttranscriptional regulation of Robo3/Rig-1 expression. (2010)
  • Author(s): Kuwako K, Kakumoto K, Imai T, Igarashi M, Hamakubo T, Sakakibara S, Tessier-Lavigne M, Okano HJ, Okano H.
  • Journal Title: Neuron. 12;67(3) Pages: 407-421
  • Peer Reviewed
• [Journal Article] The Musashi family RNA-binding proteins in stem cells. (2010)
  • Author(s): Horisawa K., Imai T, Okano H, Yanagawa H.
  • Journal Title: BioMol Concepts Vol.1 Pages: 59-66
  • Peer Reviewed
• [Journal Article] Musashil as a marker of reactive astrocytes after transient focal brain ischemia. (2010)
  • Author(s): Oki K, Kaneko N, Kanki H, Imai T, Suzuki N, Sawamoto K, Okano H.
  • Journal Title: Neurosci Res. 66 Pages: 305-309
  • Peer Reviewed
• [Journal Article] Neural RNA-binding protein Musashi1 controls midline crossing of precerebellar neurons through posttranscriptional regulation of Robo3/Rig-1 expression. (2010)
  • Author(s): Kuwako K, Kakumoto K, Imai T, Igarashi M, Hamakubo T, Sakakibara S, Tessier-Lavigne M, Okano HJ, Okano H.
  • Journal Title: Neuron Volume: 12 Pages: 407-421
  • Peer Reviewed
• [Journal Article] The Musashi family RNA-binding proteins in stem cells. (2010)
  • Author(s): Horisawa K., Imai T, Okano H, Yanagawa H
  • Journal Title: BioMol Concepts Volume: 1 Pages: 59-66
  • Peer Reviewed
• [Journal Article] Musashil as a marker of reactive astrocytes after transient focal brain ischemia. (2010)
  • Author(s): Oki K., Kaneko N., Kanki H., Imai T., Suzuki N., Sawamoto K., Okano H.
  • Journal Title: Neuroscience Research 66 Pages: 390-395
  • Peer Reviewed
• [Journal Article] 3'-Untranslated region of doublecortin mRNA is a binding target of the Musashil RNA-binding protein. (2009)
  • Author(s): Horisawa K, Imai T, Okano H, Yanagawa H.
  • Journal Title: FEBS Lett. 583(14) Pages: 2429-2434
  • Peer Reviewed
• [Journal Article] 3'-Untranslated region of doublecortin mRNA is a binding target of the Musashil RNA-binding protein. (2009)
  • Author(s): Horisawa K., Imai T., Okano H., Yanagawa H.
  • Journal Title: FEBS Letters 583 Pages: 2429-2434
  • Peer Reviewed
• [Presentation] ヒト悪性脳腫瘍癌幹細胞におけるMusashiの発現と抗腫瘍効果のメカニズム (2011)
  • Author(s): 武藤淳、今井貴雄、馬渕洋、松崎由未、吉田一成、岡野栄之
  • Organizer: 第10回日本再生医療学会総会、O-19-6、会期3/1-2
  • Place of Presentation: 京王プラザホテル・東京
  • Year and Date: 2011-03-02
• [Presentation] ヒト悪性脳腫瘍癌幹細胞におけるMusashiの発現と抗腫瘍効果のメカニズム (2011)
  • Author(s): 武藤淳、今井貴雄、馬渕洋、松崎由未、吉田一成、岡野栄之
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 京王プラザホテル・東京
  • Year and Date: 2011-03-02
• [Presentation] 神経幹細胞におけるmusashil遺伝子の転写制御解析 (2010)
  • Author(s): 河瀬聡、今井貴雄、原央子、矢口邦夫、糸原重美、岡野栄之
  • Organizer: 第33回日本神経科学会・第50回日本神経化学会・第20回神経回路学会合同年会、P1-d18、会期9/2-4
  • Place of Presentation: 神戸国際会議場・神戸
  • Year and Date: 2010-09-02
• [Presentation] 神経幹細胞におけるmusashi1遺伝子の転写制御解析 (2010)
  • Author(s): 河瀬聡、今井貴雄、原央子、矢口邦夫、糸原重美、岡野栄之
  • Organizer: 第33回日本神経科学会・第50回日本神経化学会・第20回神経回路学会合同年会
  • Place of Presentation: 神戸国際会議場・神戸
  • Year and Date: 2010-09-02
• [Presentation] Ribonomics解析によるMusashiを介したmRNA regulonの同定 (2010)
  • Author(s): 今井貴雄、河原裕憲、河瀬聡、岩成宏子、望月康弘、児玉龍彦、浜窪隆雄、岡野栄之
  • Organizer: 第12回日本RNA学会年会、P-120、会期7/27-29
  • Place of Presentation: 一橋記念講堂・東京
  • Year and Date: 2010-07-28
• [Presentation] RNA結合蛋白質Msi1と新規標的mRNAの相互作用解析 (2010)
  • Author(s): 堀澤健一、松尾薫、全井貴雄、岡野栄之、柳川弘志
  • Organizer: 第12回日本RNA学会年会、P-118、会期7/27-29
  • Place of Presentation: 一橋記念講堂・東京
  • Year and Date: 2010-07-28
• [Presentation] Ribonomics解析によるMusashiを介したmRNA regulonの同定 (2010)
  • Author(s): 今井貴雄、河原裕憲、河瀬聡、岩成宏子、望月康弘、児玉龍彦、浜窪隆雄、岡野栄之
  • Organizer: 第12回日本RNA学会年会
  • Place of Presentation: 一橋記念講堂・東京
  • Year and Date: 2010-07-28
• [Presentation] RNA結合蛋白質Msi1と新規標的mRNAの相互作用解析 (2010)
  • Author(s): 堀澤健一、松尾薫、今井貴雄、岡野栄之、柳川弘志
  • Organizer: 第12回日本RNA学会年会
  • Place of Presentation: 一橋記念講堂・東京
  • Year and Date: 2010-07-28
• [Presentation] 分化制御の鍵をにぎる翻訳抑制複合体のNMR構造機能解析 (2010)
  • Author(s): 大山貴子、永田崇、田中志穂、飯倉裕之、河原裕憲、今井貴雄、岡野栄之、山崎俊夫、片平正人
  • Organizer: 第12回日本RNA学会年会、P-119、会期7/27-29
  • Place of Presentation: 一橋記念講堂・東京
  • Year and Date: 2010-07-27
• [Presentation] 分化制御の鍵をにぎる翻訳抑制複合体のNMR構造機能解析 (2010)
  • Author(s): 大山貴子、永田崇、田中志穂、飯倉裕之、河原裕憲、今井貴雄、岡野栄之、山崎俊夫、片平正人
  • Organizer: 第12回日本RNA学会年会
  • Place of Presentation: 一橋記念講堂・東京
  • Year and Date: 2010-07-27
• [Presentation] 神経幹細胞におけるmusashi-1遺伝子の転写制御機構の解析(Analysis of transcriptional regulation of musashi-1 gene in neural stem cells) (2009)
  • Author(s): 河瀬聡, 今井貴雄, 原央子, 矢口邦雄, 糸原重美, 岡野栄之
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)4p-0004
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] Musashil新規標的doublecortinとの相互作用解析(Ihteraction analysis of the Musashil RNA-binding protein and a novel target Mrna, doublecortin) (2009)
  • Author(s): 堀澤健一, 今井貴雄, 岡野栄之, 柳川弘志
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)4P-0096
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] 翻訳制御に関わるMusashi1とPABP1の相互作用と立体構造の解析(NMR approaches to elucidate the molecular mechanism of translation inhibition by Musashil and PABP1) (2009)
  • Author(s): 飯倉裕之, 田中志穂, 樋口敬介, 河原裕憲, 今井貴雄, 岡野栄之, 永田崇, 片平正人
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)3P-0088
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] RNA結合蛋白質Musashilのlet-7 miRNA機能発現に対する制御(RNA-binding protein Musashil regulates the function of let-7 miRNAs.) (2009)
  • Author(s): 今井貴雄, 河原裕憲, 河瀬聡, 岡野栄之
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)1P-0286
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] RNA結合蛋白質Musashilのlet-7 miRNA機能発現に対する制御 (2009)
  • Author(s): 今井貴雄, 河原裕憲, 河瀬聡, 岡野栄之
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: パシフイコ横浜、横浜
  • Year and Date: 2009-12-09
• [Presentation] Acontribution of Musashil to the regulation by Lin-28 in blocking miRNA processing (2009)
  • Author(s): Hironori Kawahara, Takao Imai, Hideyuki Okano
  • Organizer: 第7回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー,東京
  • Year and Date: 2009-05-15
• [Presentation] RNA-binding protein Musashil inhibits let-7 miRNA activity (2009)
  • Author(s): Takao Imai, Hironori Kawahara, Satoshi Kawase, Hideyuki Okano.
  • Organizer: 第7回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー,東京
  • Year and Date: 2009-05-15
• [Presentation] Analysis of transcriptional regulation of musashil gene in neural stem cells (2009)
  • Author(s): Satoshi Kawase, Takao Imai, Chikako Hara, Hideyuki Okano
  • Organizer: 第7回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー,東京
  • Year and Date: 2009-05-15
• [Presentation] Analysis of Musashil function in human glioma stem cells and development of gene therapy for tumor growth suppression. (2009)
  • Author(s): Jun Muto, Takao Imai, Yumi Matsuzaki, Takeshi Kawase, Hideyuki Okano
  • Organizer: 第7回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー,東京
  • Year and Date: 2009-05-15
• [Presentation] RNA-binding protein Musashil inhibits let-7 miRNA activity. (2009)
  • Author(s): Imai T., Kawahara H., Kawase H., Okano H.
  • Organizer: 第7回幹細胞シンポジウム
  • Place of Presentation: 泉ガーデンギャラリー,東京
  • Year and Date: 2009-05-15