ncRNAのケミカルタクソノミ

2014 Fiscal Year Annual Research Report

• Project Area: Neo-taxonomy of noncoding RNAs
• Project/Area Number: 26113003
• Research Institution: The University of Tokyo
• Principal Investigator: 鈴木 勉 東京大学, 工学(系)研究科(研究院), 教授 (20292782)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: RNA修飾

Outline of Annual Research Achievements

RNAは転写後に様々な修飾を受けて本来の機能を発揮する。リボソーム生合成過程においては、RNAヘリケース、GTPase、rRNA修飾酵素などのアッセンブリー因子が重要な役割を担っていることが知られている。しかし、個々のアッセンブリー因子がどのような分子機構でリボソームの生合成に関与するかについては、不明な点が多く残されている。RlmEはS-アデノシルメチオニン(AdoMet)をメチル基供与体として、23S rRNAのHelix 92 (H92)に存在する2552位のウリジンを2'-Oメチル化 (Um2552)する修飾酵素である。RlmE及びUm2552は大腸菌からヒトに至るまで生物種間で広く保存されており、この部位の修飾が機能的、生理学的に重要な役割を担っていることを示唆している。私たちは、50Sサブユニットの後期アッセンブリー過程において、RlmEによるUm2552のたった一か所のメチル化が45S前駆体から50Sサブユニットへの成熟を促進する役割があることを示した。特に、Um2552のメチル化は、ドメインIVとVの会合を促し、L36や他のリボソームタンパク質の導入や、5S rRNAの複合体の組み込みを促進することで、45S前駆体から50Sへの生合成が進行することを示した。この成果は、rRNA修飾の作用メカニズムを示したことのみならず、アッセンブリー因子の酵素活性によるリボソーム生合成の一部を再現したという意味においても特筆すべき成果である。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

真核生物18S rRNAのac4C修飾酵素RRA1/NAT10の同定と機能解析は二報の論文として報告した。最初の論文はJBC誌におけるRNA部門のBest of 2014を受賞した。また、大腸菌リボソームの生合成過程においてrRNAメチル化修飾の役割を明確に示した成果はPNAS誌に掲載され、関係者の間で大きな反響があった。

Strategy for Future Research Activity

化学特性に基づくRNAの作動エレメントを見出すために、個々のRNA分子に含まれる修飾部位を同定する。これまでに見つかっている新規RNA修飾の構造解析を進めるとともに、RNA修飾酵素の同定や生合成機構の解析を続ける。また、修飾酵素のノックアウト細胞やマウスの表現型の解析を進めることにより、RNA修飾が担う生理学的な性質についても探求する。また、mRNAに含まれる修飾部位を網羅的に同定するための技術開発を進め、より確度の高い同定手法を確立する。

Research Products

• [Journal Article] Iron-sulfur proteins responsible for RNA modifications (2015)
  • Author(s): Kimura, S. and Suzuki, T.
  • Journal Title: Biochimica et Biophysica Acta (BBA)-Molecular Cell Research Volume: 1853 Pages: 1272-1283
  • DOI: 10.1016/j.bbamcr.2014.12.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Defining fundamental steps in the assembly of Drosophila RNAi enzyme complex (2015)
  • Author(s): Iwasaki, S., Sasaki, H. M., Sakaguchi, Y., Suzuki, T., Tadakuma, H. and Tomari, Y.
  • Journal Title: Nature Volume: 521 Pages: 533-536
  • DOI: 10.1038/nature14254
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transcriptome-wide identification of adenosine-to-inosine editing using the ICE-seq method (2015)
  • Author(s): Suzuki, T., Ueda, H., Okada, S. and Sakurai, M.
  • Journal Title: Nature Protocol Volume: 10 Pages: 715-732
  • DOI: 10.1038/nprot.2015.037
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biochemical and transcriptome-wide identification of A-to-I RNA editing sites by ICE-seq (2015)
  • Author(s): Okada, S., Sakurai, M., Ueda, H. and Suzuki, T.
  • Journal Title: Methods in Enzymol Volume: 560 Pages: 331-353
  • DOI: 10.1016/bs.mie.2015.03.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nucleoside analysis by hydrophilic interaction liquid chromatography coupled with mass spectrometry (2015)
  • Author(s): Sakaguchi, Y., Miyauchi, K., Kang, B. and Suzuki, T.
  • Journal Title: Methods in Enzymol Volume: 560 Pages: 19-28
  • DOI: 10.1016/bs.mie.2015.03.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ribosomal RNA methyltransferases contribute to Staphylococcus aureus virulence (2015)
  • Author(s): Kyuma, T., Kimura, S., Hanada, Y., Suzuki, T., Sekimizu, K. and Kaito, C.
  • Journal Title: FEBS Journal Volume: 282 Pages: 2570-2584
  • DOI: 10.1111/febs.13302
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility (2015)
  • Author(s): Shoji, T., Takaya, A., Sato, Y., Kimura, S., Suzuki, T. and Yamamoto, T.
  • Journal Title: Nucleic Acids Research Volume: 43 Pages: 8964-8972
  • DOI: 10.1093/nar/gkv609
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Destabilization of microRNA-122 in human cells by 3’ deadenylation mediated by PARN and CUGBP1 (2015)
  • Author(s): Katoh, T., Hojo, H. and Suzuki, T.
  • Journal Title: Nucleic Acids Research Volume: 43 Pages: 7521-7534
  • DOI: 10.1093/nar/gkv669
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of gene expression via retrotransposon insertions and the noncoding RNA 4.5S RNAH (2015)
  • Author(s): Ishida, K., Miyauchi, K., Kimura, Y., Mito, M., Okada, S., Suzuki, T. and Nakagawa, S.
  • Journal Title: Genes Cells Volume: 20 Pages: 887-901
  • DOI: 10.1111/gtc.12280
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia (2015)
  • Author(s): Yoshida, M., Kataoka, N., Miyauchi, K., Ohe, K., Iida, K., Yoshida, S., Nojima, T., Okuno, Y., Onogi, H., Usui, T., Takeuchi, A., Hosoya, T., Suzuki, T. and Hagiwara, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 112 Pages: 2764-2769
  • DOI: 10.1073/pnas.1415525112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs precise mitochondrial protein translation and contributes to myopathy in mice and humans (2015)
  • Author(s): Wei, F., Zhou, B., Suzuki, T., Miyata, K., Ujihara, Y., Takahashi, N., Xie, P., Michiue, H., Fujimura, A., Kaitsuka, T., Matsui, H., Koga, Y., Mohri, S., Suzuki, T., Oike, Y. and Tomizawa, K.
  • Journal Title: Cell Metabolism Volume: 21 Pages: 428-442
  • DOI: 10.1016/j.cmet.2015.01.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A single methylation of 23S rRNA triggers late steps of 50S ribosomal subunit assembly (2015)
  • Author(s): Arai, T., Ishiguro, K., Kimura, S., Sakaguchi, Y., Suzuki, T. and Suzuki, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 112 Pages: E4707-E4716
  • DOI: 10.1073/pnas.1506749112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs (2014)
  • Author(s): Suzuki, T. and Suzuki, T.
  • Journal Title: Nucleic Acids Res Volume: 42 Pages: 7346-7357
  • DOI: 10.1093/nar/gku390
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Discovery of the β-barrel-type RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs (2014)
  • Author(s): Kimura, S., Miyauchi, K., Ikeuchi, Y., Thiaville, P.C., de Crecy-Lagard, and Suzuki, T.
  • Journal Title: Nucleic Acids Res Volume: 42 Pages: 9350-9365
  • DOI: 10.1093/nar/gku618
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A single acetylation of 18S rRNA is essential for biogenesis of the small ribosomal subunit in Saccharomyces cerevisiae (2014)
  • Author(s): Ito, S., Akamatsu, Y., Noma, A., Kimura, S., Miyauchi, K., Ikeuchi, Y., Suzuki, T. and Suzuki, T.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 26201-26212
  • DOI: 10.1074/jbc.M114.593996
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18S rRNA (2014)
  • Author(s): Ito, S., Horikawa, S., Suzuki, T., Kawauchi, H., Tanaka, Y., Suzuki, T. and Suzuki, T.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 35724-35730
  • DOI: 10.1074/jbc.C114.602698
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex (2014)
  • Author(s): Takai, H., Masuda, K., Sato, T., Sakaguchi, Y., Suzuki, T., Suzuki, T., Koyama-Nasu, R., Nasu-Nishimura, Y., Katou, Y., Ogawa, H., Morishita, Y., Kozuka-Hata, H., Oyama, M., Todo, T., Ino, Y., Mukasa, A., Saito, N., Toyoshima, C., Shirahige, K. and Akiyama, T.
  • Journal Title: Cell Reports Volume: 9 Pages: 48-60
  • DOI: 10.1016/j.celrep.2014.08.071
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Convergent evolution of AUA decoding in bacteria and archaea (2014)
  • Author(s): Suzuki, T. and Numata, T.
  • Journal Title: RNA Biology Volume: 11 Pages: 1586-1596
  • DOI: 10.4161/15476286.2014.992281
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Essential RNA acetyltransferase required for ribosome biogenesis and tRNA modification (2015)
  • Author(s): Tsutomu Suzuki
  • Organizer: GRC on RNA editing and modification（招待講演）
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2015-03-09
• [Presentation] RNA修飾の多彩な機能と疾患 (2015)
  • Author(s): 鈴木 勉
  • Organizer: 埼玉医科大学ゲノム医学研究センター学術集会（招待講演）
  • Place of Presentation: 埼玉医科大学ゲノム医学研究センター、埼玉県日高市
  • Year and Date: 2015-01-27
  • Invited
• [Presentation] Mitochondrial diseases caused by deficient tRNA modifications (2014)
  • Author(s): Tsutomu Suzuki
  • Organizer: AussieMit2014（招待講演）
  • Place of Presentation: Perth, Australia
  • Year and Date: 2014-12-01
  • Int'l Joint Research / Invited
• [Presentation] A single acetylation of 18S rRNA regulates ribosome biogenesis by sensing cellular energy status (2014)
  • Author(s): Tsutomu Suzuki
  • Organizer: Joint Australia and Japan RNA meeting (JAJRNA2014)（招待講演）
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2014-11-05
  • Int'l Joint Research / Invited
• [Presentation] Biogenesis and function of cyclic t6A and derivatives (2014)
  • Author(s): Tsutomu Suzuki
  • Organizer: 25th tRNA conference（招待講演）
  • Place of Presentation: Kyllini, Greece
  • Year and Date: 2014-09-22
  • Int'l Joint Research / Invited
• [Presentation] ヒトはなぜ病気になるのでしょう？～病気の原因を分子レベルで探る～ (2014)
  • Author(s): 鈴木 勉
  • Organizer: 高校生のためのオープンキャンパス2014（招待講演）
  • Place of Presentation: 東京大学本郷キャンパス、東京都文京区
  • Year and Date: 2014-08-06
  • Invited
• [Remarks] http://rna.chem.t.u-tokyo.ac.jp/