A novel function of RNA splicing in control of proliferation and differentiation of germ cells

• Project/Area Number: 15K14451
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Kobe University
• Principal Investigator: SAKAMOTO HIROSHI 神戸大学, 理学研究科, 教授 (00187048)
• Research Collaborator: DOBASHI Takumi ; TAKASAKI Teruaki ; INOUE Kunio
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: RNA / 生殖細胞 / スプライシング制御 / 細胞増殖 / 細胞分化

Outline of Final Research Achievements

Germ cells are the only cells that undergo meiosis as well as mitosis. It is well known that the balance between self-renewal and differentiation of germ cells is strictly regulated through transcriptional and translational mechanisms, yet it remains unclear whether splicing regulation is involved in this process. We identified an SR protein kinase SPK-1 that phosphorylates splicing factors in C. elegans and found that SPK-1 is essential to maintain the proliferative state by prohibiting precocious entry into meiosis. Furthermore, our genetic analyses suggest that SPK-1 regulates a translational repressor that is known as germline tumor suppressor. Thus, we propose a novel role of splicing regulation in the control of germline proliferation.

Research Products

• [Journal Article] The Exon Junction Complex controls the efficient and faithful splicing of a subset of transcripts involved in mitotic cell-cycle progression. (2016)
  • Author(s): Fukumura, K., Wakabayashi, S., Kataoka, N., Sakamoto, H., ;Suzuki, Y., ;Nakai, K., Mayeda, A., Inoue, K.
  • Journal Title: International Journal of Molecular Sciences Volume: 17 Issue: 8 Pages: 1153-1153
  • DOI: 10.3390/ijms17081153
  • NAID: 120005838148
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Control of the heat stress-induced alternative splicing of a subset of genes by hnRNP K. (2016)
  • Author(s): Yamamoto K, Furukawa M, Fukumura K, Kawamura A, Yamada T, Suzuki H, Hirose T, Sakamoto H, Inoue K.
  • Journal Title: Genes Cells. Volume: 21 Issue: 9 Pages: 1006-1014
  • DOI: 10.1111/gtc.12400
  • Peer Reviewed
• [Journal Article] Restricted distribution of mrg-1 mRNA in C. elegans primordial germ cells through germ granule-independent regulation (2015)
  • Author(s): Miwa, T., Takasaki, T., Inoue, K., Sakamoto, H.
  • Journal Title: Genes to Cells Volume: 20 Issue: 11 Pages: 932-942
  • DOI: 10.1111/gtc.12285
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 線虫C. elegansの生殖細胞形成に必須なクロマチン制御因子群の始原生殖細胞への限局機構の解析 (2015)
  • Author(s): 巳波孝至、井上邦夫、坂本博、高崎輝恒
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸国際展示場（兵庫県・神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 線虫C. elegansの始原生殖細胞成熟過程におけるクロマチン制御機構の研究 (2015)
  • Author(s): 巳波孝至、高崎輝恒、井上邦夫、坂本博
  • Organizer: 関西地区線虫勉強会
  • Place of Presentation: 関西学院大学梅田キャンパス（大阪府・大阪市）
  • Year and Date: 2015-10-15
• [Presentation] 線虫C.elegansの生殖細胞形成に必須なクロマチン制御因子群の始原生殖細胞への限局機構の解析 (2015)
  • Author(s): 巳波孝至、高崎輝恒、井上邦夫、坂本博
  • Organizer: 第17回RNA学会年会
  • Place of Presentation: ホテルライフォート札幌（北海道・札幌市）
  • Year and Date: 2015-07-15