Genome-wide survey of translational control under microgravity

• Project/Area Number: 19K22406
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Iwasaki Shintaro 国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (80611441)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 翻訳 / Ribosome / Ribosome profiling / 重力 / ミトコンドリア / リボソーム / mRNA

Outline of Research at the Start

生命は40億年の歴史の中で、地球上の重力に適応、進化してきた。しかしその一方で生命が地球上の重力という環境をどのように利用し、遺伝子発現を制御しているのか？という問いは、基本的なものであるのに関わらず驚くべきほどよくわかっていない。本研究では、セントラルドグマの中核をなす「翻訳」が重力によってどのように影響されるか、というこれまでの生物学の歴史で全く研究されていないフロンティアに挑戦する。

Outline of Final Research Achievements

Life on the earth has evolved in a form suitable for the gravitational force (1 g). However, the molecular details of how mammalian cells harness gravity have remained unclear. Here we show that mitochondria utilize gravity for activating protein synthesis within the organelle. Genome-wide ribosome profiling unveiled the reduced mitochondrial translation in human cells under microgravity (1 × 10-6 g). In addition, we found that attenuated cell adhesion and the subsequent FAK signaling pathway by microgravity decrease the mitochondrial protein synthesis.

Academic Significance and Societal Importance of the Research Achievements

本研究により細胞が重力を利用し、エネルギーを産生するオルガネラ内の翻訳を活性化しているという機構が明らかになった。生物にとって重力が非常に重要な物理的パラメーターであることは、宇宙に長期滞在した宇宙飛行士の加齢様症状によっても明らかである。特にミトコンドリアダメージは加齢と密接に関わることが知られており、本研究で明らかになった微小重力によるミトコンドリア翻訳の減少がまさにその引き金になっている可能性を示唆する。また、細胞接着とミトコンドリア翻訳の関連はこれまで全く知られていない現象であり、新たな研究のseedを生むという意味で学術的意義は高い。

Research Products

• [Int'l Joint Research] University of California, Berkeley(米国)
• [Int'l Joint Research] University of California, Berkeley/University of California, San Francisco(米国)
• [Int'l Joint Research] University of California, Berkeley(米国)
• [Journal Article] Comprehensive identification of ribosomal collision by disome profiling (2022)
  • Author(s): 岩崎信太郎
  • Journal Title: 生化学 Volume: 94 Issue: 1 Pages: 87-91
  • DOI: 10.14952/SEIKAGAKU.2022.940087
  • ISSN: 0037-1017
  • Year and Date: 2022-02-25
• [Journal Article] Splicing modulators elicit global translational repression by condensate-prone proteins translated from introns (2022)
  • Author(s): Chhipi-Shrestha Jagat K.、Schneider-Poetsch Tilman、Suzuki Takehiro、Mito Mari、Khan Khalid、Dohmae Naoshi、Iwasaki Shintaro、Yoshida Minoru
  • Journal Title: Cell Chemical Biology Volume: 29 Issue: 2 Pages: 259-275
  • DOI: 10.1016/j.chembiol.2021.07.015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The landscape of translational stall sites in bacteria revealed by monosome and disome profiling. (2022)
  • Author(s): Fujita T, Yokoyama T, Shirouzu M, Taguchi H, Ito T, and Iwasaki S
  • Journal Title: RNA Volume: 28 Issue: 3 Pages: 290-302
  • DOI: 10.1261/rna.078188.120
  • Peer Reviewed
• [Journal Article] Ribosome slowdown triggers codon‐mediated mRNA decay independently of ribosome quality?control (2022)
  • Author(s): Mishima Yuichiro、Han Peixun、Ishibashi Kota、Kimura Seisuke、Iwasaki Shintaro
  • Journal Title: The EMBO Journal Volume: 41 Issue: 5
  • DOI: 10.15252/embj.2021109256
  • Peer Reviewed
• [Journal Article] Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells (2022)
  • Author(s): Wu Quan、Shichino Yuichi、Abe Takaya、Suetsugu Taeko、Omori Ayaka、Kiyonari Hiroshi、Iwasaki Shintaro、Matsuzaki Fumio
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 470-470
  • DOI: 10.1038/s41467-022-28097-y
  • Peer Reviewed / Open Access
• [Journal Article] Into the matrix : current methods for mitochondrial translation studies. (2022)
  • Author(s): Apostolopoulos A and Iwasaki S
  • Journal Title: J Biochem. Volume: 171 Issue: 4 Pages: 379-387
  • DOI: 10.1093/jb/mvac005
  • Peer Reviewed / Open Access
• [Journal Article] Mito-FUNCAT-FACS reveals cellular heterogeneity in mitochondrial translation (2022)
  • Author(s): Kimura Yusuke、Saito Hironori、Osaki Tatsuya、Ikegami Yasuhiro、Wakigawa Taisei、Ikeuchi Yoshiho、Iwasaki Shintaro
  • Journal Title: RNA Volume: - Issue: 6 Pages: 122-122
  • DOI: 10.1261/rna.079097.122
  • Peer Reviewed / Open Access
• [Journal Article] Mammalian HEMK1 methylates glutamine residue of the GGQ motif of mitochondrial release factors (2022)
  • Author(s): Fang Qi、Kimura Yusuke、Shimazu Tadahiro、Suzuki Takehiro、Yamada Ayumi、Dohmae Naoshi、Iwasaki Shintaro、Shinkai Yoichi
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 4104-4104
  • DOI: 10.1038/s41598-022-08061-y
  • Peer Reviewed / Open Access
• [Journal Article] Selectivity of mRNA degradation by autophagy in yeast (2021)
  • Author(s): Shiho Makino, Tomoko Kawamata, Shintaro Iwasaki, Yoshinori Ohsumi
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 2316-2316
  • DOI: 10.1038/s41467-021-22574-6
  • Peer Reviewed / Open Access
• [Journal Article] Ribosome stalling caused by the Argonaute-microRNA-SGS3 complex regulates the production of secondary siRNAs in plants (2021)
  • Author(s): Iwakawa Hiro-oki、Lam Andy Y.W.、Mine Akira、Fujita Tomoya、Kiyokawa Kaori、Yoshikawa Manabu、Takeda Atsushi、Iwasaki Shintaro、Tomari Yukihide
  • Journal Title: Cell Reports Volume: 35 Issue: 13 Pages: 109300-109300
  • DOI: 10.1016/j.celrep.2021.109300
  • Peer Reviewed / Open Access
• [Journal Article] Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons (2021)
  • Author(s): Ichihara Kazuya、Matsumoto Akinobu、Nishida Hiroshi、Kito Yuki、Shimizu Hideyuki、Shichino Yuichi、Iwasaki Shintaro、Imami Koshi、Ishihama Yasushi、Nakayama Keiichi I
  • Journal Title: Nucleic Acids Research Volume: 49 Issue: 13 Pages: 7298-7317
  • DOI: 10.1093/nar/gkab549
  • Peer Reviewed / Open Access
• [Journal Article] Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation (2021)
  • Author(s): Chadani Yuhei、Sugata Nobuyuki、Niwa Tatsuya、Ito Yosuke、Iwasaki Shintaro、Taguchi Hideki
  • Journal Title: The EMBO Journal Volume: 40 Issue: 23 Pages: 1-13
  • DOI: 10.15252/embj.2021108299
  • Peer Reviewed
• [Journal Article] eIF2B-capturing viral protein NSs suppresses the integrated stress response (2021)
  • Author(s): Kashiwagi Kazuhiro、Shichino Yuichi、Osaki Tatsuya、Sakamoto Ayako、Nishimoto Madoka、Takahashi Mari、Mito Mari、Weber Friedemann、Ikeuchi Yoshiho、Iwasaki Shintaro、Ito Takuhiro
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 7102-7102
  • DOI: 10.1038/s41467-021-27337-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spliceostatin A interaction with SF3B1 limits U1 snRNP availability and causes premature cleavage and polyadenylation. (2021)
  • Author(s): Yoshimoto, R., Chhipi-Shrestha, J.K., Schneider-Poetsch, T., Furuno, M., Burroughs, A.M., Noma, S., Suzuki, H., Hayashizaki, Y., Mayeda, A., Nakagawa, S., Kaida, D., Iwasaki, S., Yoshida, M.
  • Journal Title: Cell Chem. Biol. Volume: - Issue: 9 Pages: 1356-1365
  • DOI: 10.1016/j.chembiol.2021.03.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Pentatricopeptide Repeat Protein PGR3 Is Required for the Translation of petL and ndhG by Binding Their 5′ UTRs (2021)
  • Author(s): Higashi Haruka、Kato Yoshinobu、Fujita Tomoya、Iwasaki Shintaro、Nakamura Masayuki、Nishimura Yoshiki、Takenaka Mizuki、Shikanai Toshiharu
  • Journal Title: Plant and Cell Physiology Volume: - Issue: 7 Pages: 1-10
  • DOI: 10.1093/pcp/pcaa180
  • Peer Reviewed
• [Journal Article] Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A (2021)
  • Author(s): Chen Mingming、Asanuma Miwako、Takahashi Mari、Shichino Yuichi、Mito Mari、Fujiwara Koichi、Saito Hironori、Floor Stephen N.、Ingolia Nicholas T.、Sodeoka Mikiko、Dodo Kosuke、Ito Takuhiro、Iwasaki Shintaro
  • Journal Title: Cell Chemical Biology Volume: 28 Issue: 4 Pages: 475-486
  • DOI: 10.1016/j.chembiol.2020.11.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protocol for disome profiling to survey ribosome collision in humans and zebrafish. (2020)
  • Author(s): Mito M, Mishima Y, and Iwasaki S
  • Journal Title: STAR Protoc. Volume: 1 Issue: 3 Pages: 100168-100168
  • DOI: 10.1016/j.xpro.2020.100168
  • Peer Reviewed / Open Access
• [Journal Article] Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome (2020)
  • Author(s): Matsuki Yasuko、Matsuo Yoshitaka、Nakano Yu、Iwasaki Shintaro、Yoko Hideyuki、Udagawa Tsuyoshi、Li Sihan、Saeki Yasushi、Yoshihisa Tohru、Tanaka Keiji、Ingolia Nicholas T.、Inada Toshifumi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 19669-19669
  • DOI: 10.1038/s41598-020-76239-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complete chemical structures of human mitochondrial tRNAs (2020)
  • Author(s): Suzuki Takeo、Yashiro Yuka、Kikuchi Ittoku、Ishigami Yuma、Saito Hironori、Matsuzawa Ikuya、Okada Shunpei、Mito Mari、Iwasaki Shintaro、Ma Ding、Zhao Xuewei、Asano Kana、Lin Huan、Kirino Yohei、Sakaguchi Yuriko、Suzuki Tsutomu
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-15
  • DOI: 10.1038/s41467-020-18068-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Implications of RNG140 (caprin2)-mediated translational regulation in eye lens differentiation (2020)
  • Author(s): Kaori Nakazawa, Yuichi Shichino,Shintaro Iwasaki, and Nobuyuki Shiina
  • Journal Title: Journal of Biological Chemistry Volume: 295 Issue: 44 Pages: 15029-15044
  • DOI: 10.1074/jbc.ra120.012715
  • Peer Reviewed / Open Access
• [Journal Article] N-terminal deletion of Swi3 created by the deletion of a dubious ORF YJL175W mitigates protein burden effect in S. cerevisiae (2020)
  • Author(s): Saeki Nozomu、Eguchi Yuichi、Kintaka Reiko、Makanae Koji、Shichino Yuichi、Iwasaki Shintaro、Kanno Manabu、Kimura Nobutada、Moriya Hisao
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 9500-9500
  • DOI: 10.1038/s41598-020-66307-z
  • NAID: 120006883501
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide survey of ribosome collision. (2020)
  • Author(s): Han, P., Shichino, Y., Schneider-Poetsch, T., Mito, M., Hashimoto, S., Udagawa, T., Kohno, K., Yoshida, M., Mishima, Y., Inada, T., Iwasaki, S.
  • Journal Title: Cell Rep. Volume: 31(5) Issue: 5 Pages: 107610-107610
  • DOI: 10.1016/j.celrep.2020.107610
  • Peer Reviewed / Open Access
• [Journal Article] A Widespread Family of Heat-Resistant Obscure (Hero) Proteins Protect Against Protein Instability and Aggregation (2020)
  • Author(s): Tsuboyama K, Osaki T, Matsuura-Suzuki E, Kozuka-Hata H, Okada Y, Oyama M, Ikeuchi Y, Iwasaki S, Tomari Y
  • Journal Title: PLOS Biology Volume: 18 Issue: 3 Pages: 3000632-3000632
  • DOI: 10.1371/journal.pbio.3000632
  • Peer Reviewed / Open Access
• [Journal Article] Translational Landscape of Protein-Coding and Non-Protein-Coding RNAs upon Light Exposure in Arabidopsis (2019)
  • Author(s): Kurihara Yukio、Makita Yuko、Shimohira Haruka、Fujita Tomoya、Iwasaki Shintaro、Matsui Minami
  • Journal Title: Plant and Cell Physiology Volume: 61 Issue: 3 Pages: 536-545
  • DOI: 10.1093/pcp/pcz219
  • Peer Reviewed
• [Journal Article] Codon bias confers stability to human mRNAs (2019)
  • Author(s): Hia Fabian、Yang Sheng Fan、Shichino Yuichi、Yoshinaga Masanori、Murakawa Yasuhiro、Vandenbon Alexis、Fukao Akira、Fujiwara Toshinobu、Landthaler Markus、Natsume Tohru、Adachi Shungo、Iwasaki Shintaro、Takeuchi Osamu
  • Journal Title: EMBO reports Volume: 20 Issue: 11
  • DOI: 10.15252/embr.201948220
  • NAID: 120006767912
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Proximity RNA Labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules (2019)
  • Author(s): Padron Alejandro、Iwasaki Shintaro、Ingolia Nicholas T.
  • Journal Title: Molecular Cell Volume: 75 Issue: 4 Pages: 875-887.e5
  • DOI: 10.1016/j.molcel.2019.07.030
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Free Glycans Derived From O-mannosylated Glycoproteins Suggest the Presence of an O-glycoprotein Degradation Pathway in Yeast (2019)
  • Author(s): Hirayama H, Matsuda T, Tsuchiya Y, Oka R, Seino J , Huang C, Nakajima K , Noda Y, Shichino Y, Iwasaki S , Suzuki T
  • Journal Title: J Biol Chem Volume: 294(44) Issue: 44 Pages: 15900-15900
  • DOI: 10.1074/jbc.ra119.009491
  • Peer Reviewed / Open Access
• [Journal Article] The plant translatome surveyed by ribosome profiling (2019)
  • Author(s): Fujita Tomoya, Kurihara Yukio, Iwasaki Shintaro
  • Journal Title: Plant And Cell Physiology Volume: 印刷中 Issue: 9 Pages: 1917-1926
  • DOI: 10.1093/pcp/pcz059
  • Peer Reviewed
• [Presentation] Unexpected mRNA selectivity of translation initiation inhibitors (2022)
  • Author(s): 岩崎信太郎
  • Organizer: 文部科学省新学術領域研究 学術研究支援基盤形成 先端モデル動物支援プラットフォーム (AdAMS)成果発表会202
  • Invited
• [Presentation] リボソームプロファイリングのコツ (2021)
  • Author(s): 岩崎信太郎
  • Organizer: イルミナウェブセミナープロフェッショナルシリーズ
  • Invited
• [Presentation] Genome-wide survey of ribosome traverse (2021)
  • Author(s): 岩崎信太郎
  • Organizer: R&D戦略委員会第１回企画シンポジウム「翻訳・アミノ酸代謝調節による生体機能制御」
  • Invited
• [Presentation] 葉緑体翻訳と細胞質mRNA調節のシンクロナイゼーション (2021)
  • Author(s): 岩崎信太郎
  • Organizer: 2021年度ラン藻ゲノム交流会
  • Invited
• [Presentation] eIF2B結合性ウイルスタンパク質NSsによる統合的ストレス応答抑制 (2021)
  • Author(s): 岩崎信太郎
  • Organizer: 第94回日本生化学大会
  • Invited
• [Presentation] METTL18-mediated histidine methylation on RPL3 modulates translation elongation for proteostasis maintenance (2021)
  • Author(s): 岩崎信太郎
  • Organizer: 第15回日本臨床ストレス応答学会「マルチファセット・プロテインズ」
  • Invited
• [Presentation] A specific eIF4A paralog facilitates LARP1-mediated translation repression during mTORC1 inhibition (2021)
  • Author(s): 岩崎信太郎
  • Organizer: 第59回日本生物物理学学会年会
  • Invited
• [Presentation] A specific eIF4A paralog facilitates LARP1-mediated translation repression during mTORC1 inhibition (2021)
  • Author(s): Shintaro Iwasaki
  • Organizer: Mini-symposium on RNA Biology and Therapeutics [Basic Science (IBS) and Seoul National University (SNU), Korea]
  • Int'l Joint Research / Invited
• [Presentation] Gravity activates mitochondrial translation through cell adhesion-FAK axis (2021)
  • Author(s): Shintaro Iwasaki
  • Organizer: The 44th Annual Meeting of The Molecular Biology Society of Japan (MBSJ2021)
  • Int'l Joint Research / Invited
• [Presentation] 葉緑体翻訳と細胞質mRNA調節のシンクロナイゼーション (2021)
  • Author(s): 岩崎信太郎
  • Organizer: 第62回日本植物生理学会年会
  • Invited
• [Presentation] Genome-wide survey of ribosome collision (2019)
  • Author(s): 岩崎信太郎
  • Organizer: 第42回日本分子生物学会年会
• [Book] 相分離生物学の全貌（現代化学増刊46) RNP顆粒研究を加速するトランスクリプトーム解析技術 (2020)
  • Author(s): 七野悠一、岩崎信太郎
  • Total Pages: 5
  • Publisher: 東京化学同人
  • ISBN: 9784807913466
• [Book] 実験医学2019年11月号 リボソームプロファイリングによる網羅的翻訳解析の最前線 (2019)
  • Author(s): 木村悠介, 岩崎信太郎
  • Total Pages: 3
  • Publisher: 羊土社
  • ISBN: 9784758125253
• [Remarks]
  • URL: http://iwasakirna.com/publications.php
• [Remarks]
  • URL: https://www.riken.jp/research/labs/chief/rna_sys_biochem/index.html
• [Remarks] スプライシング調節化合物がもたらす新たな作用を発見
  • URL: https://www.riken.jp/press/2021/20210330_1/
• [Remarks] 翻訳阻害抗がん剤の二つ目の標的を同定
  • URL: https://www.riken.jp/press/2020/20201002_1/index.html
• [Remarks] ヒトミトコンドリアtRNA修飾の全体像を解明
  • URL: https://www.riken.jp/press/2020/20200831_1/index.html
• [Remarks] リボソームの交通渋滞を見つける方法
  • URL: https://www.riken.jp/press/2020/20200506_1/index.html
• [Remarks] 光受容によるタンパク質の翻訳変化を解明 －遺伝子の発現量調節への応用に期待－
  • URL: https://www.riken.jp/press/2020/20200316_1/index.html
• [Remarks] 新しい糖鎖代謝機構の発見 －未知の糖鎖分解酵素の同定への一歩－
  • URL: https://www.riken.jp/press/2019/20190711_1/
• [Patent(Industrial Property Rights)] INTEGRATED STRESS RESPONSE INHIBITOR (2021)
  • Inventor(s): Ito T, Kashiwagi K, 他
  • Industrial Property Rights Holder: Ito T, Kashiwagi K, 他
  • Industrial Property Rights Type: 特許
  • Filing Date: 2021
  • Overseas
• [Patent(Industrial Property Rights)] 非リボソームRNA含有試料の製造方法 (2020)
  • Inventor(s): 水戸麻理、岩崎信太郎
  • Industrial Property Rights Holder: 水戸麻理、岩崎信太郎
  • Industrial Property Rights Type: 特許
  • Filing Date: 2020
  • Overseas
• [Patent(Industrial Property Rights)] 非リボソームRNA含有試料の製造方法 (2019)
  • Inventor(s): Mari Mito, Shintaro Iwasaki
  • Industrial Property Rights Holder: Mari Mito, Shintaro Iwasaki
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019