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

• Project/Area Number: 25291007
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kinki 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: ¥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).

Research Products

• [Int'l Joint Research] マギル大学(カナダ)
• [Int'l Joint Research] フライブルグ大学病院(ドイツ)
• [Journal Article] Fine-tuning of translation initiation by RNA binding proteins (2016)
  • 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
• [Journal Article] Codon Usage and 3' UTR Length Determine Maternal mRNA Stability in Zebrafish (2016)
  • 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
  • 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
  • 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 proteins (2015)
  • 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
  • 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 Mechanisms (2015)
  • 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
  • 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
  • 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
• [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
• [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
  • Peer Reviewed
• [Journal Article] Defining fundamental steps in the assembly of Drosophila RNAi enzyme complex (2015)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] microRNAs trigger dissociation of eIF4AI and II from target mRNAs in human (2014)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Microbial fluorescence sensing for human neurotensin receptor type lusing Ga-engineered yeast cells (2013)
  • 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
  • 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 cerevisiae (2013)
  • 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
  • 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
  • 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
  • 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) domain (2013)
  • 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
  • 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
• [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
• [Presentation] Analysis of cell type specific translation from IRES mRNA derived from two different poliovirus strains (2015)
  • 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
• [Presentation] Analyses of the molecular function of PABP interacting protein 1 (PAIP1) in translational activation (2015)
  • 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
  • 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
• [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
  • Invited
• [Presentation] Effect of eIF4B phosphorylation by active Akt1 recruited into cap binding complex by HuD on translation (2014)
  • 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
• [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
• [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
• [Presentation] microRNAs trigger dissociation of eIF4As from target mRNAs (2014)
  • 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
• [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
• [Presentation] Analyses of cell type specific translation from the IRES mRNA derived from two different Poliovirus strains (2014)
  • 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
• [Presentation] Translational regulation by HuD through the interaction with eIF3 (2014)
  • 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
• [Presentation] Effect of eIF4B phosphorylation by active Akt1 recruited into cap binding complex by HuD on translation (2014)
  • 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
• [Presentation] 矢野雄暉、藤原俊伸 Functional relationship between HuD and Paip2 in differentiation of PC12 cells (2014)
  • 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
• [Presentation] Dissecting roles of Paip1 in HuD mediated translation activation (2014)
  • 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
• [Presentation] Novel cell free translation system using human cultured cell line (2014)
  • 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
• [Presentation] High-throughput screening approach combining siRNA reverse-transfection and reporter mRNA transfection (2014)
  • 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
• [Presentation] The mechanism of translational control which targets a translation initiation complex (2013)
  • Author(s): Akira Fukao, Nahum Sonenberg, Christian Thoma and Toshinobu Fujiwara
  • Organizer: 2013 RiboClub Annual Meeting
  • Place of Presentation: ケベック
• [Presentation] The RNA-binding protein HuD regulates cap-dependent translation by binding to the mRNA nuclear export receptor TAP/NXF1 (2013)
  • 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
• [Presentation] HuD accelerates cap-dependent translation through eIF4B phosphorylation by active Akt1 (2013)
  • 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
• [Remarks] 近畿大学薬学部生化学研究室HP
  • URL: http://www.phar.kindai.ac.jp/biochemistry/