Regulation of gene expression at mRNA level via poly A tail and its modulation by nutrient source signals

• Project/Area Number: 18K06053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: University of Tsukuba
• Principal Investigator: IRIE KENJI 筑波大学, 医学医療系, 教授 (90232628)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 酵母 / Ccr4-Not複合体 / ポリA鎖 / 遺伝子発現制御 / mRNA / Pbp1 / Ccr4 / ポリA鎖 / Pop2 / リン酸化 / グルコース

Outline of Final Research Achievements

The Ccr4-Not complex not only regulates the length of the poly A tail, but is also involved in translational repression in the steady state. We found that the phosphorylation of S39 of Pop2 by Pho85 kinase is part of the glucose sensing system. In addition, among the ccr4 and pop2 mutants, the poly A tails of the target mRNAs become longer, and Pab1 and Pbp1 bind to the longer poly A tails, resulting in excessive translation from the target mRNAs. These excessive translation confers to growth retardation, temperature-sensitive proliferation and abnormal gene expression.

Academic Significance and Societal Importance of the Research Achievements

ポリA鎖はmRNAの翻訳効率とmRNA分解に重要な役割を果たしているが、生体内におけるポリA鎖の役割については不明な点が多い。ポリA鎖を短縮させるCcr4-Not複合体とPan2-Pan3複合体の活性がどのように調節されているかも明らかではない。本研究では、これらの不明な点にアプローチする。本研究の対象は、出芽酵母であるが、Ccr4、Pop2、Dhh1、Pbp1、Puf5など本研究の対象とする分子は進化上も保存されており、ポリA鎖の長さと翻訳効率・mRNA安定性の関係の進化上普遍的な分子機構の解明につながると考えている。

Research Products

• [Journal Article] The eIF4E-binding protein Eap1 has similar but independent roles in cell growth and gene expression with the cytoplasmic deadenylase Ccr4 (2021)
  • Author(s): Higuchi Yudai、Fujii Shiori、Valderrama Arvin Lapiz、Irie Kaoru、Suda Yasuyuki、Mizuno Tomoaki、Irie Kenji
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: - Issue: 6 Pages: 1452-1459
  • DOI: 10.1093/bbb/zbab056
  • Peer Reviewed
• [Journal Article] Pbp1 mediates the aberrant expression of genes involved in growth defect of ccr4 and pop2 mutants in yeast Saccharomyces cerevisiae (2021)
  • Author(s): Valderrama Arvin Lapiz、Fujii Shiori、Duy Duong Long、Irie Kaoru、Mizuno Tomoaki、Suda Yasuyuki、Irie Kenji
  • Journal Title: Genes to Cells Volume: - Issue: 6 Pages: 381-398
  • DOI: 10.1111/gtc.12846
  • Peer Reviewed / Open Access
• [Journal Article] Pbp1, the yeast ortholog of human Ataxin-2, functions in the cell growth on non-fermentable carbon sources. (2021)
  • Author(s): Tuong Vi DT, Fujii S, Valderrama AL, Ito A, Matsuura E, Nishihata A, Irie K, Suda Y, Mizuno T, Irie K.
  • Journal Title: PLOS ONE Volume: in press Issue: 5 Pages: e0251456-e0251456
  • DOI: 10.1371/journal.pone.0251456
  • Peer Reviewed / Open Access
• [Journal Article] Snf1 AMPK positively regulates ER-phagy via expression control of Atg39 autophagy receptor in yeast ER stress response (2020)
  • Author(s): Mizuno Tomoaki、Muroi Kei、Irie Kenji
  • Journal Title: PLOS Genetics Volume: 16 Issue: 9 Pages: e1009053-e1009053
  • DOI: 10.1371/journal.pgen.1009053
  • Peer Reviewed / Open Access
• [Journal Article] Pop2 Phosphorylation at S39 Contributes to the Glucose Repression of Stress Response Genes, HSP12 and HSP26 (2019)
  • Author(s): Lien PTK, Viet NTM, Mizuno T, Suda Y, Irie K.
  • Journal Title: PLoS One Volume: 14 Issue: 4 Pages: e0215064-e0215064
  • DOI: 10.1371/journal.pone.0215064
  • NAID: 120007133492
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of LRG1 expression by RNA‐binding protein Puf5 in the budding yeast cell wall integrity pathway (2018)
  • Author(s): Viet Nguyen Thi Minh、Duy Duong Long、Saito Kazuhiro、Irie Kaoru、Suda Yasuyuki、Mizuno Tomoaki、Irie Kenji
  • Journal Title: Genes to Cells Volume: 23 Issue: 12 Pages: 988-997
  • DOI: 10.1111/gtc.12646
  • Peer Reviewed / Open Access
• [Journal Article] Induction of Ptp2 and Cmp2 protein phosphatases is crucial for the adaptive response to ER stress in Saccharomyces cerevisiae. (2018)
  • Author(s): Mizuno T, Nakamura M, Irie K.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 13078-13078
  • DOI: 10.1038/s41598-018-31413-6
  • NAID: 120007133846
  • Peer Reviewed / Open Access
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