Analysis of proteins involved in the MAT2A mRNA stability control

• Project/Area Number: 17K07278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Tohoku University
• Principal Investigator: Shima Hiroki 東北大学, 医学系研究科, 助手 (00448268)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: RNA / S-アデノシルメチオニン / N6-メチルアデノシン / 転写後調節 / RNA安定性 / RNA結合タンパク質 / 発現制御

Outline of Final Research Achievements

The expression of MAT2A, the ubiquitous S-adenosylmethionine (SAM) synthetase in mammals, is regulated in a intracellular SAM-responsive manner. The feedback control is mediated by methyl-6-adenosine (m6A) modification occurring six specific adenosine residues in the hairpins located in the 3' UTR of the MAT2A mRNA. The research aimed at identification of RNA binding proteins interacting with the MAT2A 3'UTR. By comparing associating proteins between WT and m6A-site-mutant 3'UTR, we found RNA-binding proteins involved in the stability control of the MAT2A mRNA.

Academic Significance and Societal Importance of the Research Achievements

mRNAの転写後調節は、遺伝子発現制御の主要な仕組みの一つである。m6A修飾はmRNAに見られる修飾のうち最も多いものであり、これによるRNA制御の分子メカニズムは近年の注目を集めている。本研究の結果はMAT2A mRNAを対象としてとりあげ、m6AによるRNA制御のメカニズムの理解に資するものであるとともに、m6A 制御や細胞内SAM 量調節の異常を原因とする疾患の研究のための基礎的な情報としても貢献できる可能性もある。

Research Products

• [Journal Article] N1-methyladenosine (m1A) RNA modification: the key to ribosome control (2020)
  • Author(s): Shima Hiroki、Igarashi Kazuhiko
  • Journal Title: The Journal of Biochemistry Volume: - Issue: 6 Pages: 535-539
  • DOI: 10.1093/jb/mvaa026
  • Open Access
• [Journal Article] Aurora kinase A-mediated phosphorylation of mPOU at a specific site drives skeletal muscle differentiation (2020)
  • Author(s): Karthigeyan Dhanasekan、Bose Arnab、Boopathi Ramachandran、Rao Vinay Jaya、Shima Hiroki、Bharathy Narendra、Igarashi Kazuhiko、Taneja Reshma、Trivedi Arun Kumar、Kundu Tapas K
  • Journal Title: The Journal of Biochemistry Volume: 167 Issue: 2 Pages: 195-201
  • DOI: 10.1093/jb/mvz088
  • NAID: 40022164742
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Haploinsufficient tumor suppressor Tip60 negatively regulates oncogenic Aurora B kinase (2019)
  • Author(s): ARNAB BOSE, SURABHI SUDEVAN, VINAY J RAO, HIROKI SHIMA, ARUN KUMAR TRIVEDI, KAZUHIKO IGARASHI, TAPAS K KUNDU
  • Journal Title: Journal of Biosciences Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Strategy towards tailored donor tissue-specific pancreatic islet isolation (2019)
  • Author(s): Miyazaki Yuki、Murayama Kazutaka、Fathi Ibrahim、Imura Takehiro、Yamagata Youhei、Watanabe Kimiko、Maeda Hiroshi、Inagaki Akiko、Igarashi Yasuhiro、Miyagi Shigehito、Shima Hiroki、Igarashi Kazuhiko、Kamei Takashi、Unno Michiaki、Goto Masafumi
  • Journal Title: PLOS ONE Volume: 14 Issue: 5 Pages: e0216136-e0216136
  • DOI: 10.1371/journal.pone.0216136
  • Peer Reviewed / Open Access
• [Journal Article] Lactate dehydrogenase C is required for the protein expression of a sperm-specific isoform of lactate dehydrogenase A (2018)
  • Author(s): Dodo Mina、Kitamura Hiroshi、Shima Hiroki、Saigusa Daisuke、Wati Sisca Meida、Ota Nao、Katsuoka Fumiki、Chiba Hatsune、Okae Hiroaki、Arima Takahiro、Igarashi Kazuhiko、Koseki Takeyoshi、Sekine Hiroki、Motohashi Hozumi
  • Journal Title: The Journal of Biochemistry Volume: 165 Issue: 4 Pages: 323
  • DOI: 10.1093/jb/mvy108
  • NAID: 40021893390
  • Peer Reviewed / Open Access
• [Journal Article] Target of rapamycin-signaling modulates starch accumulation via glycogenin phosphorylation status in the unicellular red alga Cyanidioschyzon merolae (2018)
  • Author(s): Pancha Imran、Shima Hiroki、Higashitani Nahoko、Igarashi Kazuhiko、Higashitani Atsushi、Tanaka Kan、Imamura Sousuke
  • Journal Title: The Plant Journal Volume: 97 Issue: 3 Pages: 485-499
  • DOI: 10.1111/tpj.14136
  • Peer Reviewed
• [Journal Article] O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1 (2018)
  • Author(s): Sekine Hiroki、Okazaki Keito、Kato Koichiro、Alam M. Morshedul、Shima Hiroki、Katsuoka Fumiki、Tsujita Tadayuki、Suzuki Norio、Kobayashi Akira、Igarashi Kazuhiko、Yamamoto Masayuki、Motohashi Hozumi
  • Journal Title: Molecular and Cellular Biology Volume: 38 Issue: 17 Pages: 00252-18
  • DOI: 10.1128/mcb.00252-18
  • Peer Reviewed / Open Access
• [Journal Article] Zinc finger-IRF composite elements bound by Ikaros/IRF4 complexes function as gene repression in plasma cell (2018)
  • Author(s): Kyoko Ochiai, Haruka Kondo, Yasunobu Okamura, Hiroki Shima, Yuko Kurokochi, Kazumi Kimura, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Katsuyuki Yui, Kengo Kinoshita and Kazuhiko Igarashi
  • Journal Title: Blood advances Volume: Apr 24;2(8) Issue: 8 Pages: 883-894
  • DOI: 10.1182/bloodadvances.2017010413
  • Peer Reviewed / Open Access
• [Journal Article] Phosphorylation of BACH1 switches its function from transcription factor to mitotic chromosome regulator and promotes its interaction with HMMR. (2018)
  • Author(s): Li J, Shima H, Nishizawa H, Ikeda M, Brydun A, Matsumoto M, Kato H, Saiki Y, Liu L, Watanabe-Matsui M, Iemura K, Tanaka K, Shiraki T, Igarashi K.
  • Journal Title: Biochemical Journal Volume: 475 Issue: 5 Pages: 981-1002
  • DOI: 10.1042/bcj20170520
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RNAメチル化によるSAM代謝制御 (2018)
  • Author(s): 島弘季 五十嵐和彦
  • Journal Title: 実験医学 Volume: 36
• [Journal Article] S -Adenosylmethionine Synthesis Is Regulated by Selective N 6 -Adenosine Methylation and mRNA Degradation Involving METTL16 and YTHDC1 (2017)
  • Author(s): Shima Hiroki、Matsumoto Mitsuyo、Ishigami Yuma、Ebina Masayuki、Muto Akihiko、Sato Yuho、Kumagai Sayaka、Ochiai Kyoko、Suzuki Tsutomu、Igarashi Kazuhiko
  • Journal Title: Cell Rep. Volume: 21 Issue: 12 Pages: 3354-3363
  • DOI: 10.1016/j.celrep.2017.11.092
  • Peer Reviewed / Open Access
• [Presentation] RNAメチル化によるS-アデノシルメチオニン量の制御機構とその意義 (2018)
  • Author(s): 島弘季 松本光代 五十嵐和彦
  • Organizer: 第91回日本生化学会大会