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Fine-tuning of translation regulation system by RNA-binding proteins

Research Project

Project/Area Number 25291007
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Molecular biology
Research InstitutionKinki University (2015)
Nagoya City University

Principal Investigator

FUJIWARA Toshinobu  近畿大学, 薬学部, 教授 (80362804)

Co-Investigator(Kenkyū-buntansha) TOMARI Yukihide  東京大学, 分子細胞生物学研究所, 教授 (90447368)
Co-Investigator(Renkei-kenkyūsha) TAKIZAWA Naoki  (公財)微生物化学研究会, 微生物化学研究所, 研究員 (50448502)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords翻訳制御 / microRNA / RNA結合タンパク質 / 翻訳 / RNA
Outline of Final Research Achievements

We showed that miRNA inhibits translation of the target mRNA in a deadenylation- and PABP-independent
manner at early time points (PNAS 2012)We next assessed the effect of miRISC on synergistic recruitment of translation initiation factors to target mRNAs by using direct biochemical assays. We show that miRISC promotes the release of both eIF4AI and eIF4AII but not eIF4E and eIF4G from target mRNAs and demonstrate that this is independent of deadenylation. Strikingly, both, the miRISC-induced release of eIF4A I and II from the cap binding complex (CBC) and the miRISC-induced inhibition of cap-dependent translation can be counteracted by the RNA binding protein HuD via a direct interaction of HuD with eIF4A. In summary, we propose that eIF4A I and II are key targets in the translation initiation control mechanisms by miRISC. These results were reported in Molecular Cell (2014).

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (42 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (18 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 15 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (21 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] マギル大学(カナダ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] フライブルグ大学病院(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Fine-tuning of translation initiation by RNA binding proteins2016

    • Author(s)
      藤原俊伸
    • Journal Title

      生化学

      Volume: 88 Issue: 1 Pages: 135-138

    • DOI

      10.14952/SEIKAGAKU.2016.880135

    • NAID

      40020753660

    • ISSN
      0037-1017
    • Year and Date
      2016-02-25
    • Related Report
      2015 Annual Research Report
  • [Journal Article] Codon Usage and 3' UTR Length Determine Maternal mRNA Stability in Zebrafish2016

    • Author(s)
      Yuichiro Mishima, Yukihide Tomari
    • Journal Title

      Molecular Cell

      Volume: 61(6) Issue: 6 Pages: 874-85

    • DOI

      10.1016/j.molcel.2016.02.027

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification and functional analysis of the pre-piRNA 3′ Trimmer in silkworms.2016

    • Author(s)
      Izumi N, Shoji K, Sakaguchi Y, Honda S, Kirino Y, Suzuki T, Katsuma S, Tomari Y
    • Journal Title

      Cell

      Volume: 164 Issue: 5 Pages: 962-973

    • DOI

      10.1016/j.cell.2016.01.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The molecular mechanism of translational control via the communication between the microRNA pathway and RNA-binding proteins2015

    • Author(s)
      Akira Fukao, Tomohiko Aoyama, Toshinobu Fujiwara
    • Journal Title

      RNA biology

      Volume: 12 Issue: 9 Pages: 922-926

    • DOI

      10.1080/15476286.2015.1073436

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regnase-1 and Roquin Regulate
a Common Element in Inflammatory mRNAs by Spatiotemporally Distinct Mechanisms2015

    • Author(s)
      Takashi Mino, Yasuhiro Murakawa, Akira Fukao, Alexis Vandenbon, Hans-Hermann Wessels, Daisuke Ori, Takuya Uehata, Sarang Tartey, Shizuo Akira, Yutaka Suzuki, Carola G. Vinuesa, Uwe Ohler,
Daron M. Standley, Markus Landthaler, Toshinobu Fujiwara, Osamu Takeuchi.
    • Journal Title

      Cell

      Volume: 161 Issue: 5 Pages: 1058-1073

    • DOI

      10.1016/j.cell.2015.04.029

    • NAID

      120005608042

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PI4K-beta and MKNK1 are regulators of hepatitis C virus IRES-dependent translation.2015

    • Author(s)
      Lupberger J, Casanova C, Fischer B, Weiss A, Fofana I, Fontaine N, Fujiwara T, Renaud M, Kopp A, Schuster C, Brino L, Baumert TF, Thoma C.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 13344-13344

    • DOI

      10.1038/srep13344

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ヒトにおけるmicroRNAが蛋白質合成を制御する機序の解明2015

    • Author(s)
      深尾亜喜良、藤原俊伸
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 64 Pages: 307-307

    • NAID

      40020592879

    • Related Report
      2015 Annual Research Report
  • [Journal Article] microRNA機構とRNA結合タンパク質による遺伝子発現制御2015

    • Author(s)
      深尾亜喜良、藤原俊伸
    • Journal Title

      細胞工学

      Volume: 34 Pages: 767-771

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The functions of microRNAs: mRNA Decay and translational repression.2015

    • Author(s)
      Iwakawa HO, *Tomari Y.
    • Journal Title

      Trends Cell Biol.

      Volume: 25 Issue: 11 Pages: 651-65

    • DOI

      10.1016/j.tcb.2015.07.011

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defining fundamental steps in the assembly of Drosophila RNAi enzyme complex2015

    • Author(s)
      Shintaro Iwasaki, Hiroshi M. Sasaki, Yuriko Sakaguchi, Tsutomu Suzuki, Hisashi Tadakuma, & Yukihide Tomari
    • Journal Title

      Nature

      Volume: NA Issue: 7553 Pages: 0-0

    • DOI

      10.1038/nature14254

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] microRNAs trigger dissociation of eIF4AI and II from target mRNAs in human2014

    • Author(s)
      Fukao A., Mishima Y., Takizawa N., Oka S., Imataka H., Pelletier J., Sonenberg N., Thoma C. and Fujiwara T.
    • Journal Title

      Molecular Cell

      Volume: 56 Issue: 1 Pages: 79-89

    • DOI

      10.1016/j.molcel.2014.09.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structural insights into the recruitment of SMRT by the corepressor SHARP under phosphorylative regulation.2014

    • Author(s)
      Mikami S, Kanaba T, Takizawa N, Kobayashi A, Maesaki R, Fujiwara T, Ito Y,Mishima M.
    • Journal Title

      Structure.

      Volume: 22 Issue: 1 Pages: 35-46

    • DOI

      10.1016/j.str.2013.10.007

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient and cost effective production of active-form human PKB using silkworm larvae.2014

    • Author(s)
      R. Maesaki, R. Satoh, M. Taoka, T. Kanaba, T. Asano, C. Fujita, T. Fujiwara, Y. Ito, T. isobe, T. Hakoshima, K. Maenaka, and M. Mishima
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 6016-6016

    • DOI

      10.1038/srep06016

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microbial fluorescence sensing for human neurotensin receptor type lusing Ga-engineered yeast cells2013

    • Author(s)
      Jun Ishii, Asami Oda, Shota Togawa, Akira Fukao, Toshinobu Fujiwara, Chiaki Ogino and Akihiko Kondo
    • Journal Title

      Analytical Biochemistry

      Volume: 446 Pages: 37-43

    • DOI

      10.1016/j.ab.2013.10.016

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The essential role for the RNA triphosphatase Cetlp in nuclear import of the mRNA capping enzyme Cetlp-Ceglp complex of Saccharomyces cerevisiae2013

    • Author(s)
      Naoki Takizawa, Toshinobu Fujiwara, Manabu Yamasaki, Ayako Saito, Akira Fukao, Akio Nomoto, Kiyobisa Mizumoto
    • Journal Title

      ProsOne

      Volume: 8(10) Issue: 10 Pages: e78000-e78000

    • DOI

      10.1371/journal.pone.0078000

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting cancer cell-specific RNA interference by siRNA delivery using a complex carrier of affibody-displaying bio-nanocapsules and liposomes.2013

    • Author(s)
      Nishimura Y, Mieda H, Ishii J, Ogino C, Fujiwara T, Kondo A.
    • Journal Title

      J Nanobiotechnology.

      Volume: 11 Issue: 1 Pages: 19-19

    • DOI

      10.1186/1477-3155-11-19

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of the second RRM domain of Nrd1, a fission yeast MAPK target RNA binding protein, and implication for its RNA recognition and regulation.2013

    • Author(s)
      Kobayashi A, Kanaba T, Satoh R, Fujiwara T, Ito Y, Sugiura R, Mishima M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 437 Issue: 1 Pages: 12-17

    • DOI

      10.1016/j.bbrc.2013.06.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Staphylococcal superantigen-like protein 10 (SSL10) inhibits blood coagulation by binding to prothrombin and factor Xa via theirγ-carboxyglutamic acid (Gla) domain2013

    • Author(s)
      Itoh S, Yokoyama R, Kamoshida G, Fujiwara T, Okada H, Takii T, Tsuji T, Fujii S, Hashizume H, Onozaki K
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 30 Pages: 21569-21580

    • DOI

      10.1074/jbc.m113.451419

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] in vitro翻訳系を用いた新規創薬ターゲット同定法2015

    • Author(s)
      藤原俊伸
    • Organizer
      BMB2015 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド (兵庫県)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ポリオウイルスの細胞種特異的なIRES依存的翻訳の解析2015

    • Author(s)
      貞廣暁利、深尾亜喜良、滝沢直己、竹内理、藤原俊伸
    • Organizer
      BMB2015 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド (兵庫県)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analysis of cell type specific translation from IRES mRNA derived from two different poliovirus strains2015

    • Author(s)
      Akitoshi Sadahiro, Akira Fukao, Naoki Takizawa, Osamu Takeuchi, Toshinobu Fujiwara
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analyses of the molecular function of PABP interacting protein 1 (PAIP1) in translational activation2015

    • Author(s)
      Aoyama T, Fukao A, Sonenberg N, Yanagiya A, Fujiwara T
    • Organizer
      Protein Synthesis and Translational Control EMBO CONFERENCE
    • Place of Presentation
      Heidelberg, Germany
    • Year and Date
      2015-09-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] microRNAは標的mRNAから翻訳開始因子eIF4A1およびeIF4AIIを解離させる2014

    • Author(s)
      藤原俊伸
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The RNA binding protein HuD can attenuate the miRISC-mediated translation repression.2014

    • Author(s)
      Fujiwara T.
    • Organizer
      Joint Australia and Japan RNA Meeting
    • Place of Presentation
      シドニー
    • Year and Date
      2014-11-02 – 2014-11-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Effect of eIF4B phosphorylation by active Akt1 recruited into cap binding complex by HuD on translation2014

    • Author(s)
      Yano Y., Fukao A., Fujiwara T.
    • Organizer
      Joint Australia and Japan RNA Meeting
    • Place of Presentation
      シドニー
    • Year and Date
      2014-11-02 – 2014-11-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Paip1はPABP依存的に翻訳を抑制する2014

    • Author(s)
      青山智彦、深尾亜喜良、藤原俊伸
    • Organizer
      RNAフロンティアミーティング2014
    • Place of Presentation
      和歌山
    • Year and Date
      2014-09-16 – 2014-09-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性型Akt1によるeIF4Bのリン酸化を介したRNA結合タンパク質HuDのcap依存的翻訳の促進2014

    • Author(s)
      矢野雄暉、深尾亜喜良、藤原俊伸
    • Organizer
      RNAフロンティアミーティング2014
    • Place of Presentation
      和歌山
    • Year and Date
      2014-09-16 – 2014-09-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] microRNAs trigger dissociation of eIF4As from target mRNAs2014

    • Author(s)
      Fujiwara T.
    • Organizer
      Cold Spring Harbor Laboratory Translational Control
    • Place of Presentation
      ニューヨーク
    • Year and Date
      2014-09-02 – 2014-09-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性型Akt1によるeIF4Bのリン酸化を介したRNA結合タンパク質HuDのcap依存的翻訳の促進2014

    • Author(s)
      矢野雄暉、深尾亜喜良、藤原俊伸
    • Organizer
      第16回 日本RNA学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analyses of cell type specific translation from the IRES mRNA derived from two different Poliovirus strains2014

    • Author(s)
      貞廣暁利、藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] Translational regulation by HuD through the interaction with eIF32014

    • Author(s)
      高辻良文、藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] Effect of eIF4B phosphorylation by active Akt1 recruited into cap binding complex by HuD on translation2014

    • Author(s)
      矢野雄暉、藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] 矢野雄暉、藤原俊伸 Functional relationship between HuD and Paip2 in differentiation of PC12 cells2014

    • Author(s)
      大塚衆志、藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dissecting roles of Paip1 in HuD mediated translation activation2014

    • Author(s)
      青山智彦、藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] Novel cell free translation system using human cultured cell line2014

    • Author(s)
      深尾亜喜良、藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] High-throughput screening approach combining siRNA reverse-transfection and reporter mRNA transfection2014

    • Author(s)
      藤原俊伸
    • Organizer
      第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
    • Place of Presentation
      長野
    • Related Report
      2013 Annual Research Report
  • [Presentation] The mechanism of translational control which targets a translation initiation complex2013

    • Author(s)
      Akira Fukao, Nahum Sonenberg, Christian Thoma and Toshinobu Fujiwara
    • Organizer
      2013 RiboClub Annual Meeting
    • Place of Presentation
      ケベック
    • Related Report
      2013 Annual Research Report
  • [Presentation] The RNA-binding protein HuD regulates cap-dependent translation by binding to the mRNA nuclear export receptor TAP/NXF12013

    • Author(s)
      Ryosuke Satoh, Akira Fukao, Akio Nomoto and Toshinobu Fujiwara
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] HuD accelerates cap-dependent translation through eIF4B phosphorylation by active Akt12013

    • Author(s)
      Yuki Yano, Akira Fukao and Toshinobu Fujiwara
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Remarks] 近畿大学薬学部生化学研究室HP

    • URL

      http://www.phar.kindai.ac.jp/biochemistry/

    • Related Report
      2015 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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