Regulation of somatic hypermutation on the immunoglobulin gene by novel functions of an RNA splicing factor

• Project/Area Number: 16K14783
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Okayama University
• Principal Investigator: KANAYAMA Naoki 岡山大学, 自然科学研究科, 准教授 (70304334)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: SRタンパク質 / スプライシング / AID / DT40 / 抗体

Outline of Final Research Achievements

The affinity of antibodies is improved by somatic hypermutation on the immunoglobulin variable region gene. Although it has been shown that AID is essential for somatic hypermutation, it remains unclear how the AID-dependent mutation machinery works. In this study, functions of SRSF1-3, which is an isoform of the RNA splicing factor SRSF1 and essential for somatic hypermutation, were analyzed using a hypermutating B cell line. Results revealed that SRSF1-3 forms a protein complex with AID, and promotes somatic hypermutation through a mechanism linked to the C-terminal region of AID.

Research Products

• [Journal Article] SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus (2017)
  • Author(s): Yuka Kawaguchi, Hiroaki Nariki, Naoko Kawamoto, Yuichi Kanehiro, Satoshi Miyazaki, Mari Suzuki, Masaki Magari, Hiroshi Tokumitsu, Naoki Kanayama
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 485 Issue: 2 Pages: 261-266
  • DOI: 10.1016/j.bbrc.2017.02.097
  • NAID: 120006425839
  • Peer Reviewed
• [Journal Article] Identification and characterization of a centrosomal protein, FOR20 as a novel S100A6 target (2017)
  • Author(s): Kyohei Sakane, Miyu Nishiguchi, Miwako Denda, Fuminori Yamagchi, Masaki Magari, Naoki Kanayama, Ryo Morishita, Hiroshi Tokumitsu
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 491 Issue: 4 Pages: 980-985
  • DOI: 10.1016/j.bbrc.2017.07.161
  • Peer Reviewed
• [Journal Article] AMP-activated protein kinase-mediated feedback phosphorylation controls the Ca2+/calmodulin (CaM) dependence of Ca2+/CaM-dependent protein kinase kinase β (2017)
  • Author(s): Akihiro Nakanishi, Naoya Hatano, Yuya Fujiwara, Arian Sha'ri, Shota Takabatake, Hiroki Akano, Naoki Kanayama, Masaki Magari, Naohito Nozaki, Hiroshi Tokumitsu
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 48 Pages: 19804-19813
  • DOI: 10.1074/jbc.m117.805085
  • Peer Reviewed
• [Presentation] 抗体遺伝子変異能力を操作できるニワトリB細胞を用いた動物細胞ディスプレイ (2017)
  • Author(s): 金山 直樹, 太田 愛美, 西山 由美子, 清木 俊雄, 植月 英智, 川口 祐加, 仲尾 祐輝, 曲 正樹, 徳光 浩
  • Organizer: 第69回 日本生物工学会大会
• [Presentation] スプライシング因子の過剰発現及び標的遺伝子配列の操作によるニワトリB細胞株における遺伝子変異の増強 (2017)
  • Author(s): 太田 愛美、西山 由美子、曲 正樹、徳光 浩、金山 直樹
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 抗体遺伝子変異の転写関連過程におけるSRSF1-3の役割の解析 (2017)
  • Author(s): 金山 直樹、川口 祐加、横山 和輝、石橋 朋之、曲 正樹、徳光 浩
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] AID発現とSHM誘導におけるBCRシグナルの役割 (2017)
  • Author(s): 梶浦 雄也、金廣 優一、曲 正樹、徳光 浩、金山 直樹
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] AID発現とSHM誘導におけるBCRシグナルの役割 (2016)
  • Author(s): 梶浦 雄也、金廣 優一、有年 由貴子、曲 正樹、徳光 浩、金山 直樹
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-02
• [Presentation] 抗体遺伝子変異における転写依存性過程におけるSRSF1-3の役割の解析 (2016)
  • Author(s): 川口 祐加、横山 和輝、河本 奈緒子、成木 弘明、松山 雄磨、金廣 優一、曲 正樹、大森 斉、徳光 浩、金山 直樹
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-02
• [Presentation] 抗体遺伝子高頻度突然変異におけるssDNA形成へのSRSF1-3の関与の解析 (2016)
  • Author(s): 横山 和輝、川口 祐加、松山 雄磨、河本 奈緒子、成木 弘明、徳光 浩、曲 正樹、金山 直樹
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-02
• [Presentation] SRSF1-3の高度保存領域が抗体遺伝子変異に寄与する (2016)
  • Author(s): 成木 弘明、川口 祐加、宮崎 誠士、河本 奈緒子、横山 和輝、徳光 浩、曲 正樹、金山 直樹
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-02
• [Presentation] SRSF1-3 has a role in nuclear localization of AID by regulating its nuclear export (2016)
  • Author(s): Kanayama, N., Kawaguchi, Y., Kawamoto, N., Nariki, H., Miyazaki, S., Yokoyama, K., Magari, M., Ohmori, H., Tokumitsu, H.
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Analysis of a role for SRSF1-3 in a transcription-coupled process during IgV hypermutation (2016)
  • Author(s): Kawaguchi, Y., Yokoyama, K., Kawamoto, N., Nariki, H., Matsuyama, Y., Kanehiro, Y., Hikasa, T., Magari, M., Ohmori, H., Tokumitsu, H., Kanayama, N.
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Remarks] 細胞機能設計学研究室
  • URL: http://www.okayama-u.ac.jp/user/saibou/index.html
• [Remarks] http://www.okayama-u.ac.jp/user/saibou/index.html