Analyses of a mechanism and physiological significance of NSD.

• Project/Area Number: 15K20947
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology; Neurochemistry/Neuropharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Hashimoto Yoshifumi 東京大学, 医科学研究所, 特任研究員 (80734540)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: NSD / NMD / RNAi / 切断型mRNA / リボソームリサイクリング / mRNA品質管理機構

Outline of Final Research Achievements

Nonstop mRNA decay (NSD) is a mechanism that immediately degrades aberrant mRNAs lacking stop codon. In this study, we attempted to reveal a mechanism of NSD in higher eukaryote and endogenous targets of NSD.
As a result, we revealed pivotal factors of NSD in higher eukaryote. Furthermore, we identified mRNA intermediates produced in other mRNA degrading mechanisms as endogenous NSD targets. These results indicate that NSD is generally required to eliminate mRNA intermediates produced in other mRNA degrading mechanisms.

Research Products

• [Journal Article] Nonstop-mRNA decay machinery is involved in the clearance of mRNA 5′-fragments produced by RNAi and NMD in Drosophila melanogaster cells. (2017)
  • Author(s): Yoshifumi Hashimotoa, Masaki Takahashia, Eri Sakotaa, Yoshikazu Nakamura
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 484 Issue: 1 Pages: 1-7
  • DOI: 10.1016/j.bbrc.2017.01.092
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Calpain mediates processing of the translation termination factor eRF3 into the IAP-binding isoform p-eRF3. (2015)
  • Author(s): Hashimoto, Y., Inagaki, H., Hoshino, S.
  • Journal Title: FEBS Letters Volume: 589 Issue: 17 Pages: 2241-2247
  • DOI: 10.1016/j.febslet.2015.06.041
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Nonstop mRNA decay machinery is crucial for the clearance of 5’-mRNA products generated by siRNA and NMD cleavage (2016)
  • Author(s): Yoshifumi Hashimotoa, Masaki Takahashia, Eri Sakotaa, Yoshikazu Nakamura
  • Organizer: RNA2016
  • Place of Presentation: 京都
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Development of an efficient Cell-SELEX to generate RNA aptamers against a cell surface protein of interest (2015)
  • Author(s): Masaki Takahashi, Yoshifumi Hashimoto, Eri Sakota, Yoshikazu Nakamura
  • Organizer: The Oligonucleotide Therapeutics Society 11th Annual Meeting
  • Place of Presentation: Stadspodia, Leiden, Netherlands
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] The fate of naturally truncated nonstop mRNA in Drosophila cells (2015)
  • Author(s): Yoshifumi Hashimoto, Masaki Takahashi, Eri Sakota, Yoshikazu Nakamura
  • Organizer: 第１７回日本RNA学会年会 (17th RNA meeting in Sapporo)
  • Place of Presentation: ホテルライフォート札幌（北海道札幌市中央区）
  • Year and Date: 2015-07-15
• [Presentation] The fate of naturally truncated nonstop mRNA in Drosophila cells (2015)
  • Author(s): Yoshifumi Hashimoto, Masaki Takahashi, Eri Sakota, Yoshikazu Nakamura
  • Organizer: 第１５回東京大学生命科学シンポジウム
  • Place of Presentation: 武田先端知ビル（東京大学本郷キャンパス・浅野地区）（東京都文京区）
  • Year and Date: 2015-06-27
• [Remarks] 東京大学医科学研究所RNA医科学社会連携研究部門ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/rnaikagaku/top.html