Molecular mechanism of regulation of mRNA stability and translation by RNA-binding proteins

• Project/Area Number: 24570192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: University of Tsukuba
• Principal Investigator: IRIE KENJI 筑波大学, 医学医療系, 教授 (90232628)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ＲＮＡ / 出芽酵母 / 細胞極性 / ＲＮＡ結合タンパク質 / 細胞壁 / ポリＡ分解酵素 / 遺伝子発現 / mＲＮＡ / 酵母 / 遺伝子発現制御 / RNA結合タンパク質 / ポリA鎖分解酵素 / mRNA / デキャッピング / ポリA分解酵素 / リボソーム

Outline of Final Research Achievements

In this study, we show that PBP1 genetically interacts with CCR4 and KHD1, which encode a cytoplasmic deadenylase and an RNA binding protein, respectively. Ccr4 and Khd1 modulate a signal from Rho1 in the cell wall integrity pathway by regulating the expression of RhoGEF and RhoGAP, and the double deletion of CCR4 and KHD1 confers severe growth defect displaying cell lysis. We found that the pbp1Δ mutation suppressed the growth defect caused by the ccr4Δ khd1Δ mutation. Then we screened novel Pbp1-interacting factors, and found that Pbp1 interacts with ribosomal proteins, Rpl12a and Rpl12b. Similarly to the pbp1Δ mutation, the rpl12aΔ and rpl12bΔ mutation also suppressed the growth defect caused by the ccr4Δ khd1Δ mutation. Our results suggest that Pbp1 is involved in the Ccr4 and Khd1-mediated regulation of cell growth through the association with Rpl12a and Rpl12b.

Research Products

• [Journal Article] ATXN2の酵母オルソログPbp1はリボソーム蛋白質と協調して細胞増殖を制御する (2014)
  • Author(s): 木村雄一、入江賢児
  • Journal Title: 医学のあゆみ Volume: 250 Pages: 225-226
• [Journal Article] Pbp1 is involved in the Ccr4 and Khd1-mediated regulation of cell growth through the association with ribosomal proteins, Rpl12a and Rpl12b. (2013)
  • Author(s): Kimura Y, Irie K, Irie K.
  • Journal Title: Eukaryotic Cell Volume: 12 Issue: 6 Pages: 864-974
  • DOI: 10.1128/ec.00370-12
  • Peer Reviewed
• [Journal Article] Brap2 Regulates Temporal Control of NF-kB Localization Mediated by Inflammatory Response (2013)
  • Author(s): Takashima 0, Tsuruta F, Kigoshi Y, Nakamura S, Kim J, Katoh MC, Fukuda T, Irie K, Chiba T.
  • Journal Title: PLoS One Volume: 8 Issue: 3 Pages: 58911-58911
  • DOI: 10.1371/journal.pone.0058911
  • Peer Reviewed
• [Journal Article] Stau1 regulates Dvl2 expression during myoblast differentiation (2012)
  • Author(s): Yamaguchi, et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Issue: 1 Pages: 427-432
  • DOI: 10.1016/j.bbrc.2011.11.133
  • Peer Reviewed
• [Presentation] 出芽酵母AMPKオルソログSnf1による小胞体ストレス応答制御機構 (2014)
  • Author(s): 増田 勇人, 水野 智亮, 入江 賢児
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] The budding yeast AMPK ortholog Snf1 negatively regulates endoplasmic reticulum stress response (2014)
  • Author(s): Yuto Masuda, Tomoaki Mizuno, Kenji Irie
  • Organizer: The 13th Joint Mini-Symposium 2014 NTU, KU and UT
  • Place of Presentation: 筑波大学健康医科学イノベーション棟８階講堂
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] Pop2 deadenylase and Dhh1 decapping activator negatively regulate LRG1 expression and maintain the yeast cell wall integrity (2014)
  • Author(s): Tetsuro Ohmori, Kenji Irie
  • Organizer: The 13th Joint Mini-Symposium 2014 NTU, KU and UT
  • Place of Presentation: 筑波大学健康医科学イノベーション棟８階講堂
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] Yuichi KIMURA and Kenji IRIE (2014)
  • Author(s): Functional analysis of translational control through Pbp1
  • Organizer: The 13th Joint Mini-Symposium 2014 NTU, KU and UT
  • Place of Presentation: 筑波大学健康医科学イノベーション棟８階講堂
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] 木村雄一，入江賢児 (2014)
  • Author(s): Functional analysis of translational control through Pbp1
  • Organizer: 酵母遺伝学フォーラム
  • Place of Presentation: 東京大学弥生講堂
  • Year and Date: 2014-09-01 – 2014-09-03
• [Presentation] 出芽酵母AMPKオルソログSnf1による小胞体ストレス応答制御機構 (2014)
  • Author(s): 増田 勇人, 水野 智亮, 入江 賢児
  • Organizer: 酵母遺伝学フォーラム
  • Place of Presentation: 東京大学弥生講堂
  • Year and Date: 2014-09-01 – 2014-09-03
• [Presentation] Functional analysis of translational control through Pbp1 (2014)
  • Author(s): 木村雄一，入江賢児
  • Organizer: 日本RNA学会
  • Place of Presentation: ウインク愛知
  • Year and Date: 2014-07-23 – 2014-07-25
• [Presentation] Ccr4とPbp1はRho GAP, Lrg1の発現制御に関わる (2012)
  • Author(s): 木村雄一、入江賢児
  • Organizer: 日本RNA学会
  • Place of Presentation: 東北大学百周年記念会館
• [Presentation] Different regulation of ROM2 and LRG1 expression by Khd1, Ccr4, Pop2, and Dhh1 in the yeast cell wall integrity pathway (2012)
  • Author(s): Xia Li, Kenji Irie
  • Organizer: 日本RNA学会
  • Place of Presentation: 東北大学百周年記念会館
• [Presentation] Post-transcriptional Regulation of Gene Expression by Khd1, Ccr4, and Pbp1 (2012)
  • Author(s): Kenji Irie, Yuichi Kimura, Xia Li, Tomoaki Mizuno
  • Organizer: RNA 2012 : The 17th Annual Meeting of the RNA Society
  • Place of Presentation: Ann Arbor, Michigan, USA
• [Remarks] 筑波大学医学医療系分子細胞生物学グループホームページ
  • URL: http://www.md.tsukuba.ac.jp/basic-med/molcellbiol/index.html