Analysis of posttranscriptional mechanisms of Regnase-1-mediated mRNA decay in innate immune system

• Project/Area Number: 25860355
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: MINO Takashi 京都大学, ウイルス研究所, 助教 (60646149)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 自然免疫 / 炎症 / サイトカイン / 転写後調節 / RNA安定性制御 / Regnase-1 / Ribosome / UPF1

Outline of Final Research Achievements

Posttranscriptional regulation that modifies mRNA stability and translation provides rapid and flexible control of gene expression and control of mRNAs stability is important for coordinating the initiation and resolution of inflammation. However, the posttranscriptional mechanisms in innate immunity remain to be clarified. This study is aiming to investigate the posttranscriptional mechanisms in innate immunity based on the roles of an RNase Regnase-1 we identified.In this study, we demonstrate that Regnase-1 localized to cytoplasm and endoplasmic reticulum (ER), but not to PB and SGs, and colocalizes with ribosome. Regnase-1 destabilized translationally active mRNAs and the helicase activity of UPF1 was required for the Regnase-1-mediated mRNA decay, similar to the decay mechanisms of nonsense mRNAs. Our findings reveal that Regnase-1 might function in recognizing the translationally active mRNA and triggering mRNA destabilizing immediately.

Research Products

• [Journal Article] Regnase-1 and Roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms (2015)
  • Author(s): Takashi Mino, Yasuhiro Murakawa, Akira Fukao, Alexis Vandenbon, Hans-Hermann Wessels, Daisuke Ori, Takuya Uehata, Sarang Tartey, Shizuo Akira, Yutaka Suzuki, Carola G. Vinuesa, Uwe Ohler, Daron M. Standley, Markus Landthaler, Toshinobu Fujiwara, Osamu Takeuchi.
  • Journal Title: Cell Volume: XX
  • NAID: 120005608042
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inhibition of DNA replication of human papillomavirus by using zinc finger-single-chain FokI dimer hybrid (2014)
  • Author(s): Takashi Mino, Tomoaki Mori, Yasuhiro Aoyama, Takashi Sera
  • Journal Title: Molecular Biotechnology Volume: 56 Issue: 8 Pages: 731-737
  • DOI: 10.1007/s12033-014-9751-3
  • Peer Reviewed
• [Journal Article] Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex (2014)
  • Author(s): Sarang Tartey, Kazufumi Matsushita, Alexis Vandenbon, Daisuke Ori, Tomoko Imamura, Takashi Mino, Daron M. Standley, Jules A. Hoffmann, Jean-Marc Reichhart, Shizuo Akira, Osamu Takeuchi
  • Journal Title: The EMBO Journal Volume: 33 Issue: 20 Pages: 2332-2348
  • DOI: 10.15252/embj.201488447
  • NAID: 120005649311
  • Peer Reviewed
• [Journal Article] Gene- and protein-delivered zinc finger–staphylococcal nuclease hybrid for inhibition of DNA replication of human papillomavirus (2013)
  • Author(s): Takashi Mino, Tomoaki Mori, Yasuhiro Aoyama, Takashi Sera
  • Journal Title: PLoS One Volume: 8 Issue: 2 Pages: e56633-e56633
  • DOI: 10.1371/journal.pone.0056633
  • Peer Reviewed
• [Journal Article] Essential Roles of K63-Linked Polyubiquitin-Binding Proteins TAB2 and TAB3 in B Cell Activaion via MAPKs. (2013)
  • Author(s): Ori D
  • Journal Title: J Immunol Volume: 190(8) Issue: 8 Pages: 4037-4045
  • DOI: 10.4049/jimmunol.1300173
  • Peer Reviewed
• [Journal Article] Critical Role of AZI2 in GM-CSF-Induced Dendritic Cell Differentiation (2013)
  • Author(s): Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O
  • Journal Title: J Immunol Volume: 190 Issue: 11 Pages: 5702-11
  • DOI: 10.4049/jimmunol.1203155
  • Peer Reviewed
• [Journal Article] Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo. (2013)
  • Author(s): Kazuya Masuda, Barry Ripley, Riko Nishimura, Takashi Mino, Osamu Takeuchi, Go Shioi, Hiroshi Kiyonari, and Tadamitsu Kishimoto
  • Journal Title: Proceeding of the National Academy of Sciences of the United States of America Volume: 110 Issue: 23 Pages: 9409-9414
  • DOI: 10.1073/pnas.1307419110
  • Peer Reviewed
• [Journal Article] Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation (2013)
  • Author(s): Uehata T, Iwasaki H, Vandenbon A, Matsushita, K, Hernandez Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O and Akira S
  • Journal Title: Cell Volume: 23;153 Issue: 5 Pages: 1036-49
  • DOI: 10.1016/j.cell.2013.04.034
  • Peer Reviewed
• [Journal Article] Post-transcriptional regulation of cytokine mRNA controls the initiation and resolution of inflammation (2013)
  • Author(s): Takashi Mino, Osamu Takeuchi
  • Journal Title: Biotechnology and Genetic Engineering Volume: 29 Issue: 1 Pages: 49-60
  • DOI: 10.1080/02648725.2013.801236
  • NAID: 120005474488
  • Peer Reviewed
• [Presentation] Regnase-1 destabilizes inflammationrelated mRNAs in a translation-dependent manner (2014)
  • Author(s): Takashi Mino, Osamu Takeuchi
  • Organizer: 2014 Annual Meeting of Japanese Society for Immunology
  • Place of Presentation: 京都府京都市
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] A novel role of Regnase-1 in the iron homeostasis and anemia (2014)
  • Author(s): Masanori Yoshinaga, Takashi Mino, Osamu Takeuchi
  • Organizer: 2014 Annual Meeting of Japanese Society for Immunology
  • Place of Presentation: 京都府京都市
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Regnase-1は翻訳に依存して炎症関連mRNAを分解する (2014)
  • Author(s): 三野享史，深尾亜喜良，藤原俊伸，竹内理
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Regnase-1 標的mRNA 配列の網羅的同定 (2014)
  • Author(s): 阿部壮岐，三野享史，村川泰裕，竹内理
  • Organizer: RNAフロンティアミーティング2014
  • Place of Presentation: 和歌山県西牟婁郡白浜町
  • Year and Date: 2014-09-16 – 2014-09-18
• [Presentation] 炎症の転写後調節におけるRegnase-1の作用機構 (2014)
  • Author(s): 三野享史
  • Organizer: 新学術領域「ゲノム支援」2014年度 拡大班会議
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2014-08-20 – 2014-08-21
• [Presentation] Regnase-1 destabilizes inflammation-related mRNAs in a translation-dependent manner (2014)
  • Author(s): Takashi Mino, Akira Fukao, Toshinobu Fujiwara, Osamu Takeuchi,
  • Organizer: RNA 2014 NAGOYA, The 16th RNA meeting of the RNA Society of Japan
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2014-07-23 – 2014-07-25
• [Presentation] Regnase-1の作用機構から探る自然免疫応答における転写後調節の解明
  • Author(s): 三野享史
  • Organizer: 新学術領域「ゲノム支援」2013年度 拡大班会議
  • Place of Presentation: 神戸ポートピアホテル(兵庫県神戸市)
• [Presentation] 自然免疫応答の転写後調節におけるRegnase-1 の作用機構
  • Author(s): 三野享史
  • Organizer: 名古屋市立大学大学院薬学研究科藤原研究室セミナー
  • Place of Presentation: 名古屋市立大学田辺通キャンパス(愛知県名古屋市)
  • Invited
• [Presentation] 自然免疫応答の転写後調節におけるRegnase-1 の作用機構
  • Author(s): 三野享史
  • Organizer: 日本化学会北海道支部 平成25年度室蘭・苫小牧地区化学講演会
  • Place of Presentation: 苫小牧工業高等専門学校(北海道苫小牧市)
  • Invited
• [Remarks] 京都大学ウイルス研究所感染防御研究分野竹内研究室ホームページ
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/Takeuchi_HP/
• [Remarks] 京都大学ウイルス研究所感染防御研究分野竹内研究室ホームページ
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/Takeuchi_HP/