Exploring novel DNA modification toward paradigm shift of epigenetics

• Project/Area Number: 23655153
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemistry related to living body
• Research Institution: The University of Tokyo
• Principal Investigator: SUZUKI Tsutomu 東京大学, 大学院・工学系研究科, 教授 (20292782)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 核酸 / 蛋白質 / 糖化学 / DNA修飾 / マススペクトロメトリー / エピゲノム / エピジェネティックス

Research Abstract

Alteration of chromatin structure caused by DNA methylation and histone modifications is closely associated with higher-ordered biological processes including development, differentiation and diseases by regulating gene expression epigenetically. In this study, we employed a high-sensitive analytical method using mass spectrometry to identify some novel DNA modified bases in mammalian genomes. The chemical structure of one of them was determined.

Research Products

• [Journal Article] A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification (2013)
  • Author(s): Miyauchi, K., Kimura, S. and Suzuki, T.
  • Journal Title: Nature Chem Biol. Volume: 9 Pages: 105-111
• [Journal Article] Decoding system for the AUA codon by tRNAIle with the UAU anticodon in Mycoplasma mobile (2013)
  • Author(s): aniguchi, T., Miyauchi, K., Nakane, D., Miyata, M., Muto, A., Nishimura, S. and Suzuki, T.
  • Journal Title: Nucleic Acids Res. Volume: 41 Pages: 2621-2631
• [Journal Article] Yokobori, S., Yamagishi, A. and Watanabe, K.* Decoding mechanism of non-universal genetic codes in Loligo bleekeri mitochondria (2013)
  • Author(s): Ohira, T., Suzuki, T., Miyauchi, K., Suzuki, T.
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 7645-7652
• [Journal Article] Crystal structure of a putative methyltransferase SAV1081 from Staphylococcus aureus (2013)
  • Author(s): Kita, S., Tanaka, Y., Hirano, N., Kimura, S., Suzuki, T., Suzuki, T., Yao, M. and Tanaka, I.
  • Journal Title: Protein & Peptide Letters Volume: 20 Pages: 530-537
• [Journal Article] A cyclic form of N^6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification (2013)
  • Author(s): Miyauchi, K., Kimura, S. and Suzuki, T.
  • Journal Title: Nature Chemical Biology Volume: 9 Issue: 2 Pages: 105-11
  • DOI: 10.1038/nchembio.1137
  • Peer Reviewed
• [Journal Article] Decoding system for the AUA codon by tRNAIle with the UAU anticodon in Myrcrplasma mobile (2013)
  • Author(s): Taniguchi T, Miyauchi K, Nakane D, Miyata M, Muto A, Nishimura S, Suzuki T
  • Journal Title: Nucleic Acids Research Volume: 41 Issue: 4 Pages: 2621-2631
  • DOI: 10.1093/nar/gks1344
  • Peer Reviewed
• [Journal Article] Decoding mechanism of non-universal genetic codes in Loligo bleekeri mitochondria (2013)
  • Author(s): Ohira T, Suzuki T (第2著者), 他5名
  • Journal Title: J . Biol. Chem Volume: 288 Issue: 11 Pages: 7645-7652
  • DOI: 10.1074/jbc.m112.439554
  • Peer Reviewed
• [Journal Article] Trmt61B is a methyltransferase responsible for1-methyladenosine at position 58 of human mitochondrial tRNAs (2012)
  • Author(s): Chujo, T. and Suzuki, T.
  • Journal Title: RNA Volume: 22 Pages: 2269-2276
• [Journal Article] Structure-function analysis of human TYW2 enzyme required for the biosynthesis of a highly modified wybutosine (yW) base inphenylalanine-tRNA (2012)
  • Author(s): Rodriguez, V., Vasudevan, S., Noma, A., Carlson, B.A., Green, J.E., Suzuki, T. and Chandrasekharappa, SC.
  • Journal Title: PLoS ONE Volume: 7(6)
• [Journal Article] LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria. (2012)
  • Author(s): Chujo, T., Ohira, T., Sakaguchi, Y., Goshima, N., Nomura, N., Nagao, A. and Suzuki, T.
  • Journal Title: Nucleic Acids Res. Volume: 40 Pages: 8033-8047
• [Journal Article] Loss of snoRNA impairs ribosomal RNA modification and causes developmental defects in zebrafish (2012)
  • Author(s): Higa-Nakamine, S., Suzuki, T., Uechi, T., Chakraborty, A., Nakajima, Y., Nakamura, M., Hirano, N., Suzuki, T. and Kenmochi, N.
  • Journal Title: Nucleic Acids Res. Volume: 40 Pages: 391-398
• [Journal Article] Base methylations in the double-stranded RNA by a fused methyltransferase bearing unwinding activity (2012)
  • Author(s): Kimura, S., Ikeuchi, Y., Kitahara, K., Sakaguchi, Y., Suzuki, T. and Suzuki, T.
  • Journal Title: Nucleic Acids Res. Volume: 40 Pages: 4071-4085
• [Journal Article] Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs (2012)
  • Author(s): Chujo, T. and Suzuki, T.
  • Journal Title: RNA Volume: 22 Issue: 12 Pages: 2269-2276
  • DOI: 10.1261/rna.035600.112
  • Peer Reviewed
• [Journal Article] Structure-function analysis of human TYW2 enzyme required for the biosynthesis of a highly modified wybutosine (yW) base in phenylalanine-tRNA. (2012)
  • Author(s): Rodriguez, V., Vasudevan, S., Noma, A., Carlson, B.A., Green, J.E., Suzuki, T. and Chandrasekharappa, SC.
  • Journal Title: PLoS ONE Volume: 7 Issue: 6 Pages: e39297-e39297
  • DOI: 10.1371/journal.pone.0039297
  • Peer Reviewed
• [Journal Article] LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria. (2012)
  • Author(s): Chujo, T., Ohira, T., Sakaguchi, Y., Goshima, N., Nomura, N., Nagao, A. and Suzuki, T.
  • Journal Title: Nucleic Acids Res. Volume: 40 Issue: 16 Pages: 8033-8047
  • DOI: 10.1093/nar/gks506
  • Peer Reviewed
• [Journal Article] Base methylations in the double-stranded RNA by a fused methyltransferase bearing unwinding activity (2012)
  • Author(s): Kimura S., Ikeuchi Y., Kitahara K., Sakaguchi Y., Suzuki T., Suzuki T.
  • Journal Title: Nucleic Acids Research Volume: (掲載確定)(印刷中) Issue: 9 Pages: 4071-4085
  • DOI: 10.1093/nar/gkr1287
  • Peer Reviewed
• [Journal Article] Molecular basis of dihydrouridine formation on tRNA (2011)
  • Author(s): Yu, F., Tanaka, Y., Yamashita, K., Suzuki, T., Nakamura, A., Hirano, N., Suzuki, T., Yao, M. and Tanaka, I.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 108 Pages: 19593-19598
• [Journal Article] Crystallization and preliminary X-ray diffraction analysis of an archaeal tRNA modificationenzyme TiaS complexed with tRNAIle2 and ATP (2011)
  • Author(s): Osawa, T., Inanaga, H., Kimura, S., Terasaka, N., Suzuki, T. and Numata, T.
  • Journal Title: Acta Crystallograph Sect F Struct Biol Cryst Commun. Volume: 67 Pages: 1414-1416
• [Journal Article] Structural basis of tRNA agmatinylation essential for AUA codon decoding (2011)
  • Author(s): Osawa, T., Kimura, S., Terasaka, N., Inanaga, H., Suzuki, T. and Numata, T.
  • Journal Title: Nature Struct Mol Biol. Volume: 18 Pages: 1275-1280
• [Journal Article] Biogenesis of 2-agmatinylcytidine catalyzed by the dual protein and RNA kinase TiaS (2011)
  • Author(s): Terasaka, N., Kimura, S., Osawa, T., Numata, T. and Suzuki, T.
  • Journal Title: Nature Struct Mol Biol. Volume: 18 Pages: 1268-1274
• [Journal Article] Taurine-containing uridine modifications in tRNA anticodons are required to decipher non-universal genetic codes inascidian (2011)
  • Author(s): Suzuki, T., Miyauchi, K., Suzuki, T., Yokobori, S., Shigi, N., Kondow, A., Takeuchi,N., Yamagishi, A. and Watanabe, K.
  • Journal Title: J. Biol. Chem. Volume: 286 Pages: 35494-35498
• [Journal Article] Human mitochondrial tRNAs: biogenesis, function, structural aspects and diseases (2011)
  • Author(s): Suzuki, T., Nagao, A. and Suzuki, T.
  • Journal Title: Annu Rev Genet. Volume: 45 Pages: 299-329
• [Journal Article] Deficit of Lys-tRNA Modification by Cdkal1Causes the Development of Type 2 Diabetes inMice (2011)
  • Author(s): Wei, F., Suzuki, T., Watanabe, S., Kimura, S., Kaistuka, T., Fujimura, A., Matsui, H., Atta, M., Fontecave, M., Yamagata, K., Suzuki, T. and Tomizawa, K.
  • Journal Title: J. Clin. Invest. Volume: 121 Pages: 3598-608
• [Journal Article] Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast (2011)
  • Author(s): Ohira, T. and Suzuki, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 108 Pages: 10502-10507
• [Journal Article] Actin-binding protein ABP140 is a methyltransferase responsible for3-methylcytidine at position 32 of tRNAs inSaccharomyces cerevisiae (2011)
  • Author(s): Noma, A., Yi, S., Katoh, T., Takai, Y., Suzuki, T. and Suzuki, T.
  • Journal Title: RNA Volume: 17 Pages: 1111-1119
• [Journal Article] Loss of ribosomal RNA modification causes developmental defects in zebrafish (2011)
  • Author(s): Higa-Nakamine S, Suzuki T (第2著者) 他7名
  • Journal Title: Nucleic Acids Research Volume: 40 Issue: 1 Pages: 391-398
  • DOI: 10.1093/nar/gkr700
  • Peer Reviewed
• [Journal Article] Molecular basis of dihydrouridine formation on tRNA (2011)
  • Author(s): Yu F, Tanaka Y, Yamashita K, Suzuki T (第4著者), 他4名
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Issue: 49 Pages: 19593-19598
  • DOI: 10.1073/pnas.1112352108
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary X-ray diffraction analysis of an archaeal tRNA modification enzyme TiaS complexed with tRNA^<Ile2> and ATP (2011)
  • Author(s): Osawa, T., Inanaga, H., Kimura, S., Terasaka, N., Suzuki, T., Numata T.
  • Journal Title: Acta Crystallograph Sect F Struct Biol Cryst Commun Volume: 67 Issue: 11 Pages: 1414-1416
  • DOI: 10.1107/s1744309111034890
  • Peer Reviewed
• [Journal Article] Structural basis of tRNA agmatinylation essential for AUA codon decoding (2011)
  • Author(s): Osawa T., Kimura S., Terasaka N., Inanaga H., Suzuki T.
  • Journal Title: Nature Structural & Molcular Biology Volume: 18 Issue: 11 Pages: 1275-1280
  • DOI: 10.1038/nsmb.2144
  • Peer Reviewed
• [Journal Article] Biogenesis of 2-agmatinylcytidine catalyzed by the dual protein and RNA kinase TiaS (2011)
  • Author(s): Terasaka N., Kimura S., Osawa T., Numata T., Suzuki T.
  • Journal Title: Nature Structural & Molecular Biology Volume: 18 Issue: 11 Pages: 1268-1274
  • DOI: 10.1038/nsmb.2121
  • Peer Reviewed
• [Journal Article] Taurine-containing uridine modifications in tRNA anticodons are required to decipher non-universal genetic codes in ascidian mitochondria (2011)
  • Author(s): Suzuki T (第1著者), 他8名
  • Journal Title: J. Biol. Chem Volume: 286 Issue: 41 Pages: 35494-35498
  • DOI: 10.1074/jbc.m111.279810
  • Peer Reviewed
• [Journal Article] Deficit of tRNA(Lys) modification by Cdkall causes the development of type 2 diabetes in mice (2011)
  • Author(s): Wei FY., Suzuki T., Watanabe S., Kimura S., Kaitsuka T., Fujimura A., Matsui H., Atta M., Michiue H., Fontecave M., Yamagata K., Suzuki T., Tomizawa K.
  • Journal Title: The Journal of Clinical Investigation Volume: 121 Issue: 9 Pages: 3598-3608
  • DOI: 10.1172/jci58056
  • Peer Reviewed
• [Journal Article] Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast (2011)
  • Author(s): Ohira, T. and Suzuki, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Issue: 26 Pages: 10502-10507
  • DOI: 10.1073/pnas.1105645108
  • Peer Reviewed
• [Journal Article] Actin-binding protein ABP140 is a methyltransferase for 3-methylcytidine at position 32 of tRNAs in Saccharomyces cerevisiae (2011)
  • Author(s): Noma A, Yi S, Katoh T, Takai Y, Suzuki T and Suzuki T
  • Journal Title: RNA Volume: 17 Issue: 6 Pages: 1111-1119
  • DOI: 10.1261/rna.2653411
  • Peer Reviewed
• [Journal Article] Human mitochondrial diseases caused by lack of taurine-modification in mitochondrial tRNAs (2011)
  • Author(s): Suzuki T, Nagao A and Suzuki T
  • Journal Title: Wiley Interdiscip Rev RNA Volume: 2 Issue: 3 Pages: 376-386
  • DOI: 10.1002/wrna.65
  • Peer Reviewed
• [Presentation] RNAエピジェネティクスと生命現象 (2013)
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 滋賀
  • Year and Date: 2013-03-22
• [Presentation] RNA修飾の多彩な機能と生命現象 (2013)
  • Organizer: 武田薬品湘南研究所セミナー
  • Place of Presentation: 藤沢
  • Year and Date: 2013-03-13
• [Presentation] Molecular pathogenesis ofhuman diseases associated with RNAmodification disorder (2012)
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] A cyclic form ofN6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification (2012)
  • Organizer: XXIV tRNA Conference
  • Place of Presentation: Olmue, Chile
  • Year and Date: 2012-12-04
• [Presentation] Discovery and functional analysis of novel RNA modifications (2012)
  • Organizer: Invited Seminar in Beijing Institute of Genetics
  • Place of Presentation: 北京
  • Year and Date: 2012-10-15
• [Presentation] The cyclic form of N6-threonylcarbamoyladenosine (ct6A) as a bona fide hyper-modification of tRNAs in bacteria, lower eukaryotes and plants (2012)
  • Organizer: Cold Spring Harbor Asia Conference RNA biology
  • Place of Presentation: 中国、蘇州
  • Year and Date: 2012-10-10
• [Presentation] RNAとタンパク質をリン酸化する酵素の発見-RNA修飾の生合成と遺伝暗号の解読機構- (2012)
  • Organizer: 酵素工学研究会第68回講演会
  • Place of Presentation: 東京
  • Year and Date: 2012-10-05
• [Presentation] The cyclic form ofN6-threonylcarbamoyladenosine (ct6A) as a bona fide hyper-modification of tRNAs in bacteria, lower eukaryotes and plants (2012)
  • Organizer: FEBS International Workshop: New Developments in RNA Biology
  • Place of Presentation: ポルトガル、タビラ
  • Year and Date: 2012-09-02
• [Presentation] RNA modifications asnaturally-selected chemical diversity involved in various biological processes (2011)
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] ミトコンドリア脳筋症とtRNAのタウリン修飾欠損 (2011)
  • Organizer: 第223回川崎医学会講演会
  • Place of Presentation: 倉敷
  • Year and Date: 2011-11-29
• [Presentation] RNA修飾の多彩な機能と生命現象 (2011)
  • Organizer: 宮崎大学医学部講演会
  • Place of Presentation: 宮崎
  • Year and Date: 2011-11-24
• [Presentation] Biogenesis and function of 2-agmatinylcytidine found at the wobble position of archaeal tRNAIle (2011)
  • Organizer: ISNAC2011第38回国際核酸化学シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2011-11-11
• [Presentation] RNAマススペクトロメトリー (2011)
  • Organizer: ヒューマンサイエンス財団セミナー
  • Place of Presentation: 東京
  • Year and Date: 2011-10-06
• [Presentation] RNA修飾の生合成から細胞内の化学反応を学ぶ (2011)
  • Organizer: 日生体機能関連化学部会「若手フォーラム」
  • Place of Presentation: つくば
  • Year and Date: 2011-09-11
• [Presentation] マイクロRNAと核酸医薬のマススペクトロメトリー (2011)
  • Organizer: バイオロジカルマススペクトロメトリー2011
  • Place of Presentation: 箱根
  • Year and Date: 2011-07-11
• [Presentation] マイクロRNAと核酸医薬のマススペクトロメトリー (2011)
  • Author(s): 鈴木 勉
  • Organizer: バイオロジカルマススペクトロメトリー2011(招待講演)
  • Place of Presentation: 箱根
• [Presentation] RNA修飾の生合成から細胞内の化学反応を学ぶ (2011)
  • Author(s): 鈴木 勉
  • Organizer: 生体機能関連化学部会「若手フォーラム」(招待講演)
  • Place of Presentation: つくば
• [Presentation] RNAマススペクトロメトリー (2011)
  • Author(s): 鈴木 勉
  • Organizer: ヒューマンサイエンス財団セミナー(招待講演)
  • Place of Presentation: 東京
• [Presentation] Biogenesis and function of 2-agmatinylcytidine found at the wobble position of archaeal tRNAIle (2011)
  • Author(s): Tsutomu Suzuki
  • Organizer: ISNAC2011 第38回国際核酸化学シンポジウム(招待講演)
  • Place of Presentation: 札幌
• [Presentation] RNA修飾の多彩な機能と生命現象 (2011)
  • Author(s): 鈴木 勉
  • Organizer: 宮崎大学医学部講演会(招待講演)
  • Place of Presentation: 宮崎
• [Presentation] ミトコンドリア脳筋症とtRNAのタウリン修飾欠損 (2011)
  • Author(s): 鈴木 勉
  • Organizer: 第223回川崎医学会講演会(招待講演)
  • Place of Presentation: 倉敷
• [Presentation] RNA modifications as naturally-selected chemical diversity involved in various biological processes (2011)
  • Author(s): Tsutomu Suzuki
  • Organizer: 第34回日本分子生物学会年会(招待講演)
  • Place of Presentation: 横浜
• [Presentation] 「RNAエピジェネティクスと生命現象
  • Author(s): 鈴木 勉
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 立命館大学びわこ・くさつキャンパス(滋賀)
  • Invited
• [Presentation] RNA修飾の多彩な機能と生命現象
  • Author(s): 鈴木 勉
  • Organizer: 武田薬品湘南研究所セミナー
  • Place of Presentation: 武田薬品湘南研究所(藤沢)
  • Invited
• [Presentation] Molecular pathogenesis of human diseases associated with RNA modification disorder
  • Author(s): 鈴木 勉
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡)
  • Invited
• [Presentation] A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification
  • Author(s): Tsutomu Suzuki
  • Organizer: XXIV tRNA Conference
  • Place of Presentation: Olmue, Chile
  • Invited
• [Presentation] Discovery and functional analysis of novel RNA modifications
  • Author(s): Tsutomu Suzuki
  • Organizer: Invited Seminar in Beijing Institute of Genetics
  • Place of Presentation: Beijing, China
  • Invited
• [Presentation] The cyclic form of N6-threonylcarbamoyladenosine (ct6A) as a bona fide hyper-modification of tRNAs in bacteria, lower eukaryotes and plants
  • Author(s): Tsutomu Suzuki
  • Organizer: Cold Spring Harbor Asia Conference RNA biology
  • Place of Presentation: Suzhou, China
  • Invited
• [Presentation] RNAとタンパク質をリン酸化する酵素の発見―RNA修飾の生合成と遺伝暗号の解読機構―
  • Author(s): 鈴木 勉
  • Organizer: 酵素工学研究会第68回講演会
  • Place of Presentation: 東大本郷キャンパス（東京）
  • Invited
• [Presentation] The cyclic form of N6-threonylcarbamoyladenosine (ct6A) as a bona fide hyper-modification of tRNAs in bacteria, lower eukaryotes and plants
  • Author(s): Tsutomu Suzuki
  • Organizer: FEBS International Workshop: New Developments in RNA Biology
  • Place of Presentation: Tavira, Portugal
  • Invited
• [Remarks]
  • URL: http://www.t.u-tokyo.ac.jp/epage/release/2012/12122001.html
• [Remarks]
  • URL: http://release.nikkei.co.jp/detail.cfm-relID=326829&lindID=5
• [Remarks]
  • URL: http://first.lifesciencedb.jp/archives/6418EssentialtRNAmodificationstandsinthespotlight
• [Remarks]
  • URL: http://59.106.161.11/en/todai-research/research-news/essential-trna-modification-stands-in-the-spotlight/
• [Remarks] タンパク質合成に必須なtRNAの修飾構造を解明 -40年前に決定された化学構造は分解物であった-
  • URL: http://www.t.u-tokyo.ac.jp/epage/release/2012/12122001.html
• [Remarks] 東大、タンパク質合成に必須なtRNAの新規修飾構造を発見・解明
  • URL: http://release.nikkei.co.jp/detail.cfm?relID=326829&lindID=5
• [Remarks] タンパク質合成に必須なtRNA修飾の化学構造が決定された
  • URL: http://first.lifesciencedb.jp/archives/6418
• [Remarks] Essential tRNA modification stands in.....
  • URL: http://59.106.161.11/en/todai-research/research-news/essential-trna-modification-stands-in-the-spotlight/