Functional roles of initiator methionine tRNA

• Project/Area Number: 17K07746
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Tokyo Women's Medical University (2018-2020); University of Tsukuba (2017)
• Principal Investigator: Hirota Keiko 東京女子医科大学, 医学部, 講師 (00375370)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 線虫 / 分子遺伝学 / tRNA / 寿命

Outline of Final Research Achievements

Genetic information is transcribed into mRNA and translated into protein on ribosomes, and finally, its function is exerted. In recent years, it has been reported that knockdown of translation-initiating proteins exhibits longevity, implying a correlation between the decrease in translation efficiency and lifespan extension. Translation initiation requires association of the initiator methionine tRNA with the 40S ribosome containing the translation initiation proteins. This study revealed that the initiator methionine tRNA is methylated in Caenorhabditis elegans and clarified its physiological function.

Academic Significance and Societal Importance of the Research Achievements

DNAに書き込まれた遺伝情報は、mRNAに転写され、その後、リボソーム上でtRNAと協働してタンパク質に翻訳されて、その機能が発揮される。開始メチオニンtRNAは、翻訳の開始に必須であり、その機能を解明することは、遺伝情報の発現を介して、様々な生理現象に繋がる可能性がある。本研究において、開始メチオニンtRNAがメチル化修飾を受けることを見出し、その生理機能の一端を明らかにすることができた。今後、遺伝子発現制御に有用な情報となると期待される。

Research Products

• [Journal Article] Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans. (2019)
  • Author(s): Hada Kazumasa、Hirota Keiko、Inanobe Ai、Kako Koichiro、Miyata Mai、Araoi Sho、Matsumoto Masaki、Ohta Reiya、Arisawa Mitsuhiro、Daitoku Hiroaki、Hanada Toshikatsu、Fukamizu Akiyoshi
  • Journal Title: J. Biol. Chem. Volume: 294 Issue: 9 Pages: 3091-3099
  • DOI: 10.1074/jbc.ra118.004726
  • NAID: 120007133475
  • Peer Reviewed
• [Journal Article] rRNA adenine methylation requires T07A9.8 gene as rram-1 in Caenorhabditis elegans (2018)
  • Author(s): Yokoyama Wataru、Hirota Keiko、Wan Huahua、Sumi Naoaki、Miyata Mai、Araoi Sho、Nomura Naoto、Kako Koichiro、Fukamizu Akiyoshi
  • Journal Title: J. Biochem. Volume: 印刷中 Issue: 6 Pages: 465-474
  • DOI: 10.1093/jb/mvy018
  • NAID: 40021579911
  • Peer Reviewed / Open Access
• [Journal Article] The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans (2018)
  • Author(s): Araoi Sho、Daitoku Hiroaki、Yokoyama Atsuko、Kako Koichiro、Hirota Keiko、Fukamizu Akiyoshi
  • Journal Title: J. Biochem. Volume: 印刷中 Issue: 5 Pages: 433-440
  • DOI: 10.1093/jb/mvy012
  • NAID: 40021555333
  • Peer Reviewed
• [Presentation] The role of phosphoethanolamine methyltransferase-1 in regulating the lifespan of Caenorhabditis elegans (2020)
  • Author(s): HIROTA Keiko, KATADA Eriko, ISHIHARA Seiji, KOJIMA Mariko, KAKO Koichiro, FUKAMIZU Akiyoshi
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] T07A9.8 is required for the m1A modification at position 674 in 26S rRNA in C. elegans (2019)
  • Author(s): Hirota K., Yokoyama W., Wan H., Sumi N., Miyata M., Araoi S., Nomura N., Kako K., and Fukamizu A.
  • Organizer: 22nd International C. elegans Conference
  • Int'l Joint Research
• [Presentation] Dietary methionine influences the establishment of the germ stem cell pool mediated by sams-1 (2018)
  • Author(s): Hirota K., Yamauchi R., Kojima M., Zhao X., Miyata M., Kako K., Fukamizu A.
  • Organizer: Asia-Pacific Worm Meeting
  • Int'l Joint Research