Regulation of energy homeostasis by mRNA deadenylase complex in the liver

• Project/Area Number: 21890047
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: MORITA Masahiro The University of Tokyo, 医科学研究所, 特任研究員 (50549475)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000); Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000); Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
• Keywords: 遺伝子 / 発現制御 / Deadenylation / マイクロアレイ / 糖尿病 / 脂質代謝 / 国際情報交換 / カナダ / 脂質

Research Abstract

Obesity is a life-threatening factor and is often associated with dysregulation of gene expression. The molecular mechanism underlying the development of obesity is largely unknown. In this research project, we showed that CCR4-NOT deadenylase complex plays a key role in energy metabolism. We also identified target mRNAs of CCR4-NOT complex in the liver. Furthermore, we solved the structure of CNOT6L and CNOT7 protein. These findings may be useful to understand the mechanism of the development of obesity.

Research Products

• [Journal Article] CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death. (2011)
  • Author(s): Kentaro Ito, Takeshi Inoue, Kazumasa Yokoyama, Masahiro Morita, Toru Suzuki, Tadashi Yamamoto
  • Journal Title: Genes to Cells 16 Pages: 368-379
  • Peer Reviewed
• [Journal Article] CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death. (2011)
  • Author(s): Kentaro Ito, Takeshi Inoue, Kazumasa Yokoyama, Masahiro Morita, Toru Suzuki, Tadashi Yamamoto
  • Journal Title: Genes to Cells Volume: 16 Pages: 368-379
  • Peer Reviewed
• [Journal Article] Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity. (2010)
  • Author(s): Hui Wang, Masahiro Morita, Xiuna Yang, Toru Suzuki, Wen Yang, Jiao Wang, Kentaro Ito, Quan Wang, Cong Zhao, Mark Bartlam, Tadashi Yamamoto, Zihe Rao
  • Journal Title: EMBO Journal 29 Pages: 2566-2576
  • Peer Reviewed
• [Journal Article] Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity. (2010)
  • Author(s): Hui Wang, Masahiro Morita, Xiuna Yang, Toru Suzuki, Wen Yang, Jiao Wang, Kentaro Ito, Quan Wang, Cong Zhao, Mark Bartlam, Tadashi Yamamoto, Zihe Rao
  • Journal Title: The EMBO journal Volume: 29 Pages: 2566-2576
  • Peer Reviewed
• [Journal Article] Involvement of the CCR4-NOT Deadenylase Complex in the Control of Cell Growth. (2009)
  • Author(s): Masahiro Morita, Kentaro Ito, Toru Suzuki, Tadashi Yamamoto
  • Journal Title: Systems Biology Pages: 229-237
  • Peer Reviewed
• [Presentation] CNOT7 deficiency affects protein association and activities of murine Ccr4-Not deadenylase complex, leading to abnormal spermatogenesis (2010)
  • Author(s): Yan ZHANG, Masahiro Morita, Toru Suzuki, Tadashi Yamamoto
  • Organizer: 第33回 日本分子生物学会 年会、第83回 日本生化学会 大会 合同大会
  • Year and Date: 2010-12-09
• [Presentation] Involvement of Tob2 in adipocyte differentiation (2010)
  • Author(s): 高橋明格,森田斉弘,鈴木亨,山本雅
  • Organizer: 第33回 日本分子生物学会 年会、第83回 日本生化学会 大会 合同大会
  • Year and Date: 2010-12-09
• [Presentation] CNOT7 deficiency affects protein association and activities of murine Ccr4-Not deadenylase complex, leading to abnormal spermatogenesis (2010)
  • Author(s): Yan ZHANG, Masahiro Morita, Toru Suzuki, Tadashi Yamamoto
  • Organizer: 第33回日本分子生物学会年会,第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] Involvement of Tob2 in adipocyte differentiation (2010)
  • Author(s): 高橋明格, 森田斉弘、鈴木亨,山本雅
  • Organizer: 第33回日本分子生物学会年会,第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] Cnot3, a Novel Critical Regulator of a mRNA Stability, is Involved in the Maintenance of the Bone Mass and the Bone Structure in Senile Osteoporosis Model (2010)
  • Author(s): Chiho Watanabe, Masahiro Morita, Yoichi Ezura, Tetsuya Nakamoto, Tadayoshi Hayata, Hiroaki Hemmi, Takuya Notomi, Keiji Moriyama, Tadashi Yamamoto, Masaki Noda
  • Organizer: The American Society for Bone and Mineral Research 2010 Annual Meeting
  • Place of Presentation: Toronto
  • Year and Date: 2010-10-18
• [Presentation] Cnot3, a Novel Critical Regulator of a mRNA Stability, is Involved in the Maintenance of the Bone Mass and the Bone Structure in Senile Osteoporosis Model (2010)
  • Author(s): Chiho Watanabe, Masahiro Morita, Yoichi Ezura, Tetsuya Nakamoto, Tadayoshi Hayata, Hiroaki Hemmi, Takuya Notomi, Keiji Moriyama, Tadashi Yamamoto, Masaki Noda
  • Organizer: The American Society for Bone and Mineral Research 2010 Annual Meeting
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2010-10-18
• [Presentation] A critical role of deadenylase-mediated mRNA degradation in energy metabolism. (2010)
  • Author(s): Masahiro Morita, Yuichi Oike, Tadashi Yamamoto
  • Organizer: 第42回 日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-16
• [Presentation] A critical role of deadenylase-mediated mRNA degradation in energy metabolism (2010)
  • Author(s): Masahiro Morita, Yuichi Oike, Tadashi Yamamoto
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜 長良川国際会議場
  • Year and Date: 2010-07-16
• [Presentation] Critical involvement of deadenylase-mediated mRNA degradation in energy metabolism. (2009)
  • Author(s): Masahiro Morita, Yuichi Oike, Takeshi Nagashima, Toru Suzuki, Mariko Hatakeyama, Tadashi Yamamoto
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] CNOT1 and CNOT2 are essential for maintaining the structural integrity and the deadenylase activity of the CCR4-NOT complex (2009)
  • Author(s): Kentaro Ito, Masahiro Morita, Toru Suzuki, Tadashi Yamamoto
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] Critical involvement of deadenylase-mediated mRNA degradation in energy metabolism (2009)
  • Author(s): 森田斉弘
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] Anti-proliferative protein Tob is relevant to RNA metabolism and facilitates the interaction between P-body and stress granule.
  • Author(s): Shinichi Ogawa, Masahiro Morita, Tsuyoshi Inoue, Toru Suzuki, Tadashi Yamamoto
• [Remarks] ホームページ等