Mechanism of CCR4-NOT complex-mediated target mRNA degradation in B cells

• Project/Area Number: 15K19127
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Inoue Takeshi 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (80466838)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: B細胞分化 / CCR4-NOT複合体 / mRNA分解 / 免疫グロブリン遺伝子再構成 / 免疫学 / CCR4-NOT

Outline of Final Research Achievements

The CCR4-NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. We have previously found a severe impairment of early B cell development in mice lacking CNOT3 subunit of this complex. Here, we analyzed the underlying molecular mechanisms, and our data suggested that the CCR4-NOT complex regulates B cell differentiation by controlling Igh rearrangement and destabilizing p53 mRNA.

Research Products

• [Journal Article] Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice (2017)
  • Author(s): Masato Ogura, Takeshi Inoue, Junko Yamaki, Miwako K. Homma, Tomohiro Kurosaki, Yoshimi Homma
  • Journal Title: Eur J Immunol Volume: 47 Issue: 2 Pages: 406-418
  • DOI: 10.1002/eji.201646342
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulated selection of germinal center cells into the memory B cell compartment. (2016)
  • Author(s): Shinnakasu, R., Inoue, T., Kometani, K., Moriyama, S., Adachi, Y., Nakayama, M., Takahashi, Y., Fukuyama, H., Okada, T.,Kurosaki,T.
  • Journal Title: Nat. Immunol. Volume: 17 Issue: 7 Pages: 861-9
  • DOI: 10.1038/ni.3460
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability. (2015)
  • Author(s): Takeshi Inoue, Masahiro Morita, Atsushi Hijikata, Yoko Fukuda-Yuzawa, Shungo Adachi, Kyoichi Isono, Tomokatsu Ikawa, Hiroshi Kawamoto, Haruhiko Koseki, Tohru Natsume, Taro Fukao, Osamu Ohara, Tadashi Yamamoto, Tomohiro Kurosaki
  • Journal Title: Journal of Experimental Medicine Volume: 212 Issue: 9 Pages: 1465-1479
  • DOI: 10.1084/jem.20150384
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Distinct germinal center selection at local sites shapes memory B cell response to viral escape. (2015)
  • Author(s): Yu Adachi, Taishi Onodera, Yuki Yamada, Rina Daio, Makoto Tsuiji, Takeshi Inoue, Kazuo Kobayashi, Tomohiro Kurosaki, Manabu Ato, Yoshimasa Takahashi
  • Journal Title: Journal of Experimental Medicine Volume: 212 Issue: 10 Pages: 1709-1723
  • DOI: 10.1084/jem.20142284
  • Peer Reviewed / Open Access
• [Journal Article] RNA分解酵素複合体CCR4-NOTによるB細胞分化制御 (2015)
  • Author(s): 井上 毅
  • Journal Title: 臨床免疫・アレルギー科 Volume: 64 Pages: 585-589
  • NAID: 40020684125
• [Presentation] 胚中心B細胞におけるFOXO1転写因子の機能解析 (2016)
  • Author(s): 井上 毅
  • Organizer: 第8回シグナルネットワーク研究会
  • Place of Presentation: 大阪大学
  • Year and Date: 2016-05-27
• [Presentation] B細胞におけるCNOT3の機能解析 (2016)
  • Author(s): 井上 毅
  • Organizer: 第４回 CCR4-NOT研究会
  • Place of Presentation: 秋田
  • Year and Date: 2016-02-12