Analysis of immune regulatory mechanisms mediated by mRNA metabolism

• Project/Area Number: 18H05278
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section H
• Research Institution: Kyoto University
• Principal Investigator: 竹内 理 京都大学, 医学研究科, 教授 (10379092)
• Co-Investigator(Kenkyū-buntansha): 植畑 拓也 京都大学, 医学研究科, 助教 (50785970) ; 三野 享史 京都大学, 医学研究科, 助教 (60646149)
• Project Period (FY): 2018-06-11 – 2023-03-31
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥193,570,000 (Direct Cost: ¥148,900,000、Indirect Cost: ¥44,670,000); Fiscal Year 2022: ¥33,280,000 (Direct Cost: ¥25,600,000、Indirect Cost: ¥7,680,000); Fiscal Year 2021: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2020: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2019: ¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000); Fiscal Year 2018: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
• Keywords: 免疫応答 / mRNA分解 / mRNA修飾 / サイトカイン / 自然免疫応答 / mRNA制御 / ｍRNA分解 / 免疫制御

Outline of Annual Research Achievements

Regnase-1がTLRやIL1β刺激依存性にどのような複合体を形成し機能するかを明らかにするために、Regnase-1のInteractome解析を行った。その結果、これらの刺激に対して、Regnase-1がプロテアソームによる分解に関わるβTRCPに加え、14-3-3タンパク質と結合することを明らかにした。質量分析によるリン酸化部位解析と検証の結果、Regnase-1のS494, S513リン酸化がRegnase-1と14-3-3の結合に必須であることが明らかとなった。βTRCPと14-3-3はRegnase-1とそれぞれ異なる複合体を形成した。14-3-3と結合したRegnase-1は、βTRCPによる分解から守られているにも関わらず標的mRNA分解が障害されており、この理由として、Regnase-1の核ー細胞質のシャトリングを14-3-3が阻害しているものと考えられた。実際、S513変異により14-3-3と結合しないRegnase-1を持つ変異マウスは、βTRCPによる分解が亢進していたが、TLR刺激によるサイトカイン産生に変化を認めなかった。このように、本研究から、炎症刺激によるRegnase-1のリン酸化修飾や結合タンパク質変化によるダイナミックな制御が行われていることが明らかとなった（Akaki K. eLIFE 2021）。また、TANKはTLRシグナルを負に制御するアダプター分子として以前報告してきたが、加えて、核酸認識特にRNAではなくDNAを細胞内で認識してSTING依存性にI型インターフェロンを産生する経路の抑制にも重要であることを解明した（Wakabayashi A. Life Sci Alliance 2021）。Regnase-1自己mRNA標的核酸医薬の開発を行った(Tse C. Sci Transl Med. In Press)。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Regnase-1の動的複合体の解析やその機能解明に関し論文を発表した他、共同研究でRegnase-1ファミリーの構造解析論文(Garg A et al. Nucleic Acids Res. 2021)を発表するなど、mRNA安定性制御の分子基盤解明における研究が順調に進展している。また、Regnase-1制御法開発も進展しており、In vivoにおける効果も確認している。さらに、TLR制御に関わる新規分子Cyclin Jを同定しその分子機構やIn vivoでの免疫制御における役割も明らかにした（Chong YK et al. Science Signaling In press）。このように、本研究はこれまで順調に進展していると言える。

Strategy for Future Research Activity

1．mRNA 3’ UTRを介した免疫細胞時空間制御機構の解析：これまでの研究から、Regnase-1が核と細胞質をダイナミックに行き来することがその機能発現に重要であることが明らかとなってきた。核内でRegnase-1と結合するタンパク質を同定し、そのRegnase-1による機能発現における役割を解析し、分子機構の解明を行っていく。また、Regnase-1制御法の開発についても、継続し、特にヒト細胞における機能解析を行う。
2．コドンに隠された新たな免疫応答分子制御機構の解析：コドンの最適性に依存してmRNA安定化を制御する新規分子をスクリーニングにより同定しており、この分子の免疫細胞特異的コンディショナルノックアウトマウスを作製に成功している。本年度は、免疫細胞分化、活性化における役割を検討する。また、この分子がコドン依存性にmRNA安定性を制御するか、同定した結合タンパク質との関連を解析するとともに、Ribosomeプロファイリング解析を行い蛋白質翻訳制御の観点から
解析する。
3. mRNAエピトランスクリプトームを介した免疫制御機構の解明：mRNAのm6aメチル化修飾の免疫細胞における役割解明するため、関連分子の免疫細胞特異的ノックアウトマウス作製に成功しており、免疫細胞における役割が明らかとなりつつある。そこで、そのマウスを用いたIn vivoでのmRNA修飾の役割を明らかにするとともに、標的mRNAの網羅的同定を通じて、制御メカニズムを明らかにする。

Assessment Rating

Interim Assessment Comments (Rating)

A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.

Research Products

• [Int'l Joint Research] Strasbourg University(フランス)
• [Int'l Joint Research] MDC(ドイツ)
• [Int'l Joint Research] Stanford University(米国)
• [Int'l Joint Research] Weizmann Institute of Science(イスラエル)
• [Int'l Joint Research] ULM University(ドイツ)
• [Int'l Joint Research] MDC(ドイツ)
• [Int'l Joint Research] ULM University/MDC Berlin(ドイツ)
• [Int'l Joint Research] Stanford University/Chicago University(米国)
• [Int'l Joint Research] Strasbourg University(フランス)
• [Journal Article] Cyclin J-CDK complexes limit innate immune responses by reducing proinflammatory changes in macrophage metabolism (2022)
  • Author(s): Yee Kien Chong, Sarang Tartey, Yuki Yoshikawa, Koshi Imami, Songling Li, Masanori Yoshinaga, Ai Hirabayashi, Guohao Liu, Yutaka Suzuki, Osamu Takeuchi, et al.
  • Journal Title: Science Signaling Volume: 15
  • DOI: 10.1126/scisignal.abm5011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhancement of Regnase-1 expression with stem-loop-targeting antisense oligonucleotides alleviates inflammatory diseases (2022)
  • Author(s): Ka Man Tse, Alexis Vandenbon, Xiaotong Cui, Takashi Mino, Takuya Uehata, Keiko Yasuda, Ayuko Sato, Tohru Tsujimura, Fabian Hia, Masanori Yoshinaga, Makoto Kinoshita, Tatsusada Okuno, Osamu Takeuchi
  • Journal Title: Science Translational Medicine Volume: In Press
  • Peer Reviewed
• [Journal Article] TANK prevents IFN-dependent fatal diffuse alveolar hemorrhage by suppressing DNA-cGAS aggregation (2021)
  • Author(s): Wakabayashi Atsuko、Yoshinaga Masanori、Takeuchi Osamu
  • Journal Title: Life Science Alliance Volume: 5
  • DOI: 10.26508/lsa.202101067
  • Peer Reviewed / Open Access
• [Journal Article] IRAK1-dependent Regnase-1-14-3-3 complex formation controls Regnase-1-mediated mRNA decay (2021)
  • Author(s): Kotaro Akaki, Kosuke Ogata, Yuhei Yamauchi, Noriki Iwai, Ka Man Tse, Fabian Hia, Atsushi Mochizuki, Yasushi Ishihama, Takashi Mino, Osamu Takeuchi
  • Journal Title: eLife Volume: 10
  • DOI: 10.7554/elife.71966
  • NAID: 120007166024
  • Peer Reviewed / Open Access
• [Journal Article] Posttranscriptional regulation of ILC2 homeostatic function via tristetraprolin (2021)
  • Author(s): Hikichi Yuki、Motomura Yasutaka、Takeuchi Osamu、Moro Kazuyo
  • Journal Title: Journal of Experimental Medicine Volume: 218
  • DOI: 10.1084/jem.20210181
  • Peer Reviewed
• [Journal Article] Regnase-1-related endoribonucleases in health and immunological diseases (2021)
  • Author(s): Takashi Mino, Osamu Takeuchi
  • Journal Title: Immunological Reviews Volume: 304 Pages: 97-110
  • DOI: 10.1111/imr.13023
  • Peer Reviewed
• [Journal Article] Post-transcriptional regulation of immunological responses by Regnase-1-related RNases (2021)
  • Author(s): Uehata Takuya、Takeuchi Osamu
  • Journal Title: International Immunology Volume: 33 Pages: 859-865
  • DOI: 10.1093/intimm/dxab048
  • Peer Reviewed
• [Journal Article] Extracellular mRNA transported to the nucleus exerts translation-independent function (2021)
  • Author(s): Tomita Takeshi、Kato Masayoshi、Mishima Taishi、Matsunaga Yuta、Sanjo Hideki、Ito Ken-ichi、Minagawa Kentaro、Matsui Toshimitsu、Oikawa Hiroyuki、Takahashi Satoshi、Takao Toshifumi、Iwai Noriki、Mino Takashi、Takeuchi Osamu、Maru Yoshiro、Hiratsuka Sachie
  • Journal Title: Nat Commun. Volume: 12 Pages: 1-19
  • DOI: 10.1038/s41467-021-23969-1
  • Peer Reviewed / Open Access
• [Journal Article] PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases (2021)
  • Author(s): Garg Ankur、Roske Yvette、Yamada Shinnosuke、Uehata Takuya、Takeuchi Osamu、Heinemann Udo
  • Journal Title: Nucleic Acids Research Volume: 49 Pages: 5369-5381
  • DOI: 10.1093/nar/gkab316
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Profibrotic function of pulmonary group 2 innate lymphoid cells is controlled by Regnase-1 (2020)
  • Author(s): Yoshinari Nakatsuka, Ai Yaku, Tomohiro Handa, Alexis Vandenbon, Yuki Hikichi, Yasutaka Motomura, Yutaka Suzuki, Takuya Uehata, Takashi Mino, Tohru Tsujimura, Kazuyo Moro, Osamu Takeuchi, et al.
  • Journal Title: European Respiratory Journal Volume: 57 Pages: 2000018-2000018
  • DOI: 10.1183/13993003.00018-2020
  • Peer Reviewed
• [Journal Article] Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis (2020)
  • Author(s): Kakiuchi Nobuyuki et al.
  • Journal Title: Nature. Volume: 577 Pages: 260-265
  • DOI: 10.1038/s41586-019-1856-1
  • NAID: 120006777064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The transcription factor E2A activates multiple enhancers that drive Rag expression in developing T and B cells (2020)
  • Author(s): Miyazaki Kazuko、Watanabe Hitomi、Yoshikawa Genki、Chen Kenian、Hidaka Reiko、Aitani Yuki、Osawa Kai、Takeda Rie、Ochi Yotaro、Tani-ichi Shizue、Uehata Takuya、Takeuchi Osamu、Ikuta Koichi、Ogawa Seishi、Kondoh Gen、Lin Yin C.、Ogata Hiroyuki、Miyazaki Masaki
  • Journal Title: Science Immunology, Volume: 5 Pages: 1455-1455
  • DOI: 10.1126/sciimmunol.abb1455
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Zinc Finger Protein St18 Protects against Septic Death by Inhibiting VEGF-A from Macrophages (2020)
  • Author(s): Maruyama Kenta、Kidoya Hiroyasu、Takemura Naoki、Sugisawa Erika、Takeuchi Osamu、Kondo Takeshi、Eid Mohammed Mansour Abbas、Tanaka Hiroki、Martino Mika?l M.、Takakura Nobuyuki、Takayama Yasunori、Akira Shizuo、Vandenbon Alexis、Kumagai Yutaro
  • Journal Title: Cell Rep Volume: 32 Pages: 107906-107906
  • DOI: 10.1016/j.celrep.2020.107906
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effects of codon bias and optimality on mRNA and protein regulation (2020)
  • Author(s): Fabian Hia, Osamu Takeuchi
  • Journal Title: Cellular and Molecular Life Sciences Volume: 78 Pages: 1909-1928
  • DOI: 10.1007/s00018-020-03685-7
  • Peer Reviewed
• [Journal Article] RNA Recognition and Immunity-Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms (2020)
  • Author(s): Takuya Uehata, Osamu Takeuchi
  • Journal Title: Cells Volume: 9 Pages: 1701-1701
  • DOI: 10.3390/cells9071701
  • Peer Reviewed / Open Access
• [Journal Article] Live-Cell Imaging of Protein Degradation Utilizing Designed Protein-Tag Mutant and Fluorescent Probe with Turn-Off Switch (2020)
  • Author(s): Gao J, Hori Y, Takeuchi O, Kikuchi K
  • Journal Title: Bioconjugate Chemistry Volume: 31 Pages: 577-583
  • DOI: 10.1021/acs.bioconjchem.9b00696
  • Peer Reviewed
• [Journal Article] N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation. (2019)
  • Author(s): Yamasoba D, Sato K, Ichinose T, Imamura T, Koepke L, Joas S, Reith E, Hotter D, Misawa N, Akaki K, Uehata T, Mino T, Miyamoto S, Noda T, Yamashita A, Standley DM, Kirchhoff F, Sauter D, Koyanagi Y, Takeuchi O.
  • Journal Title: Nat Microbiol. Volume: 4 Pages: 1532-1544
  • DOI: 10.1038/s41564-019-0460-3
  • NAID: 120006731123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Translation-dependent unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs. (2019)
  • Author(s): Mino, T., Iwai, N., Endo, M., Inoue, K., Akaki, K., Hia, F., Uehata, T., Emura, T., Hidaka, K., Suzuki, Y., Standley, D. M., Okada-Hatakeyama, M., Ohno, S., Sugiyama, H., Yamashita, A., Takeuchi, O.
  • Journal Title: Nucleic Acids Research Volume: 47 Pages: 8838-8859
  • DOI: 10.1093/nar/gkz628
  • NAID: 120006708220
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Codon bias confers stability to human mRNAs (2019)
  • Author(s): Hia Fabian、Yang Sheng Fan、Shichino Yuichi、Yoshinaga Masanori、Murakawa Yasuhiro、Vandenbon Alexis、Fukao Akira、Fujiwara Toshinobu、Landthaler Markus、Natsume Tohru、Adachi Shungo、Iwasaki Shintaro、Takeuchi Osamu
  • Journal Title: EMBO reports Volume: 20
  • DOI: 10.15252/embr.201948220
  • NAID: 120006767912
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements (2019)
  • Author(s): Hirabayashi Shigeki、Bhagat Shruti、Matsuki Yu、Takegami Yujiro、Uehata Takuya、Kanemaru Ai、Itoh Masayoshi、Shirakawa Kotaro、Takaori-Kondo Akifumi、Takeuchi Osamu、Carninci Piero、Katayama Shintaro、Hayashizaki Yoshihide、Kere Juha、Kawaji Hideya、Murakawa Yasuhiro
  • Journal Title: Nature Genetics Volume: 51 Pages: 1369-1379
  • DOI: 10.1038/s41588-019-0485-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post‐transcriptional control of immune responses and its potential application (2019)
  • Author(s): Yoshinaga Masanori、Takeuchi Osamu
  • Journal Title: Clinical & Translational Immunology Volume: 8
  • DOI: 10.1002/cti2.1063
  • NAID: 120006784407
  • Peer Reviewed
• [Journal Article] RNA binding proteins in the control of autoimmune diseases (2019)
  • Author(s): Yoshinaga Masanori、Takeuchi Osamu
  • Journal Title: Immunological Medicine Volume: 42 Pages: 53-64
  • DOI: 10.1080/25785826.2019.1655192
  • Peer Reviewed
• [Journal Article] Hassall’s corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus (2019)
  • Author(s): Wang Jianwei、Sekai Miho、Matsui Takeshi、Fujii Yosuke、Matsumoto Mitsuru、Takeuchi Osamu、Minato Nagahiro、Hamazaki Yoko
  • Journal Title: International Immunology Volume: 31 Pages: 127-139
  • DOI: 10.1093/intimm/dxy073
  • NAID: 120007164929
  • Peer Reviewed / Open Access
• [Journal Article] N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation (2019)
  • Author(s): Yamasoba D, Sato K, Ichinose T, Imamura T, Koepke L, Joas S, Reith E, Hotter D, Misawa N, Akaki K, Uehata T, Mino T, Miyamoto S, Noda T, Yamashita A, Standley DM, Kirchhoff F, Sauter D, Koyanagi Y, Takeuchi O.
  • Journal Title: Nature Microbiology Volume: 印刷中
  • NAID: 120006731123
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Translation of Hepatitis A Virus IRES Is Upregulated by a Hepatic Cell-Specific Factor (2018)
  • Author(s): Sadahiro Akitoshi、Fukao Akira、Kosaka Mio、Funakami Yoshinori、Takizawa Naoki、Takeuchi Osamu、Duncan Kent E.、Fujiwara Toshinobu
  • Journal Title: Front Genet. Volume: 9 Pages: 1-10
  • DOI: 10.3389/fgene.2018.00307
  • NAID: 120006534584
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post-transcriptional regulation of immune responses by RNA binding proteins (2018)
  • Author(s): MINO Takashi、TAKEUCHI Osamu
  • Journal Title: Proc. Jpn. Acad., Ser. B Volume: 94 Issue: 6 Pages: 248-258
  • DOI: 10.2183/pjab.94.017
  • NAID: 130007395766
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia. (2018)
  • Author(s): Nakatsuka, Y., Vandenbon, A., Mino, T., Yoshinaga, M., Uehata, T., Cui, X., Sato, A., Tsujimura, T., Suzuki, Y., Sato, A., Handa, T., Chin, K., Sawa, T., Hirai, T., Takeuchi, O.
  • Journal Title: Mucosal Immunology Volume: AOP Pages: 1203-1218
  • DOI: 10.1038/s41385-018-0024-5
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Post-transcriptional regulation of innate immunity by Regnase-1 (2021)
  • Author(s): Osamu Takeuchi
  • Organizer: The 27th International Symposium on Molecular Cell Biology of Macrophages
  • Int'l Joint Research / Invited
• [Presentation] Antiviral innate immunity targeting RNA (2021)
  • Author(s): Osamu Takeuchi
  • Organizer: European Congress Immunology (ECI) 2021
  • Int'l Joint Research / Invited
• [Presentation] 炎症によるmRNA制御を介した免疫細胞分化運命決定の調節機構 (2021)
  • Author(s): 竹内理
  • Organizer: 第73回日本細胞生物学会大会
  • Invited
• [Presentation] mRNA分解による免疫制御と疾患 (2021)
  • Author(s): 竹内理
  • Organizer: 第36回 Wakoワークショップ
  • Invited
• [Presentation] 免疫細胞制御における翻訳とmRNA分解 (2021)
  • Author(s): 竹内理
  • Organizer: 日本分子生物学会年会
  • Invited
• [Presentation] Manipulation of Regnase-1 mRNA stability by antisense oligonucleotides alleviates inflammatory responses in pulmonary and autoimmune diseases (2021)
  • Author(s): Ka Man Tse, Xiaotong Cui, Alexis Vandenbon, Keiko Yasuda, Takuya Uehata, Ayuko Sato, Tohru Tsujimura, Masanori Yoshinaga, Tatsusada Okuno, Yoshinari Nakatsuka, Osamu Takeuchi
  • Organizer: KAI International Meeting 2021
  • Int'l Joint Research
• [Presentation] Lymphoid-myeloid cell fateLymphoid-Myeloid cell fate determination by endoribonucleases Regnase-1 and -3 (2021)
  • Author(s): Takuya Uehata, Shinnosuke Yamada, Masaki Miyazaki, Amir Giladi, Alexis Vandenbon, Ido Amit, Hiroshi Kawamoto, Osamu Takeuchi
  • Organizer: MMCB2020+1
  • Int'l Joint Research
• [Presentation] Manipulation of Regnase-1 mRNA stability by morpholino-based antisense oligonucleotides alleviates inflammatory responses in pulmonary and autoimmune diseases (2021)
  • Author(s): Ka Man Tse, Xiaotong Cui, Alexis Vandenbon, Keiko Yasuda, Takuya Uehata, Ayuko Sato, Tohru Tsujimura, Takashi Mino, Masanori Yoshinaga, Tatsusada Okuno, Yoshinari Nakatsuka, Osamu Takeuchi
  • Organizer: 第22回日本RNA学会年会
• [Presentation] Unexpected role of atypical cyclin in mediating macrophage functionality via metabolic regulation (2021)
  • Author(s): Yee Kien Chong, Sarang Tartey, Osamu Takeuchi
  • Organizer: The 27th International Symposium on Molecular Cell Biology of Macrophages
  • Int'l Joint Research
• [Presentation] 赤芽球分化を制御する新規転写後調節機構の解明 (2021)
  • Author(s): 吉永正憲、竹内理
  • Organizer: 第44回日本分子生物学年会
• [Presentation] Manipulating the expressions of Regnase-1 by stem-loop-targeting-antisense oligonucleotides to counteract inflammatory diseases (2021)
  • Author(s): Ka Man Tse, Xiaotong Cui, Alexis Vandenbon, Takashi Mino, Takuya Uehata, Keiko Yasuda, Ayuko Sato, Tohru Tsujimura, Fabian Hia, Masanori Yoshinaga, Osamu Takeuchi
  • Organizer: 第44回日本分子生物学年会
• [Presentation] Regnase-1/-3-Nfkbiz制御軸が造血幹細胞における細胞分化の方向性を調節する (2021)
  • Author(s): Takuya Uehata, Daisuke Ori, Masaki Miyazaki, Amir Giladi, Hiroshi Kawamoto, Ido Amit, Osamu Takeuchi
  • Organizer: 第44回日本分子生物学会年会
• [Presentation] Manipulating the expression of Regnase-1 by antisense oligonucleoties to counteract inflammatory diseases (2021)
  • Author(s): Ka Man Tse, Takashi Mino, Takuya Uehata, Keiko Yasuda, Masanori Yoshinaga, Osamu Takeuchi
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] Unexpected role of atypical cyclin in mediating macrophage functionality via metabolic regulation (2021)
  • Author(s): Yee Kien Chong, Osamu Takeuchi
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] Deciphering the role of Regnase-1 in the pathophysiology of pulmonary arterial hypertension (2021)
  • Author(s): Ai Yaku, Yusuke Manabe, Osamu Takeuchi
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] Post-transcriptional regulation of hematopoietic stem and progenitor cell lineage priming by Rnases Regnase-1/-3 via Nfkbiz mRNA decay (2021)
  • Author(s): Takuya Uehata, Daisuke Ori, Masaki Miyazaki, Amir Giladi, Tomokatsu Ikawa, Hiroshi Kawamoto, Ido Amit, Osamu Takeuchi
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] 炎症におけるRNA制御の分子基盤 (2021)
  • Author(s): 三野享史
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] RNA代謝による自然免疫応答の惹起と制御 (2020)
  • Author(s): 竹内理
  • Organizer: 日本臨床免疫学会
  • Invited
• [Presentation] Regulatory mechanisms of innate immune responses (2020)
  • Author(s): Osamu Takeuchi
  • Organizer: FIMSA Immunology course-2020
  • Int'l Joint Research / Invited
• [Presentation] Immune regulation by translation-dependent mRNA decay (2020)
  • Author(s): Osamu Takeuchi
  • Organizer: MBSJ2020
  • Invited
• [Presentation] Regnase-1による免疫調節機構 (2020)
  • Author(s): 竹内理
  • Organizer: 第7回免疫セミナー
  • Invited
• [Presentation] RNA分解による免疫応答の制御機構 (2020)
  • Author(s): 竹内理
  • Organizer: 2020年度東京大学医科学研究所国際共同利用・共同研究拠点成果報告会
  • Invited
• [Presentation] Manipulation of Regnase-1 mRNA stability alleviates inflammatory responses in diseased models (2020)
  • Author(s): Tse, K.M., Cui, X., Uehata, T., Takeuchi, O
  • Organizer: MBSJ2020
  • Invited
• [Presentation] Codon Bias Confers Stability to mRNAs in Humans, The 25th Annual Meeting of the RNA Society (2020)
  • Author(s): Hia, F., Yang, S.F., Shichino, Y., Yoshinaga, M., Murakawa, Y., Vandenbon, A., Fukao, A., Fujiwara, T., Landthaler, M., Natsume, T., Adachi, S., Iwasaki, S., Takeuchi, O.
  • Organizer: RNA2020
  • Int'l Joint Research
• [Presentation] Manipulation of Regnase-1 mRNA stability alleviates inflammatory responses in diseased models (2020)
  • Author(s): Tse, K.M., Cui, X., Uehata, T., Takeuchi, O.
  • Organizer: RNA2020
  • Int'l Joint Research
• [Presentation] LYMPHOID-MYELOID CELL FATE DETERMINATION BY ENDORIBONUCLEASES REGNASE-1 AND -3 (2020)
  • Author(s): Takuya, U., Yamada, S., Miyazaki, M., Giladi, A., Vandenbon, A., Amit, I., Kawamoto, H., Takeuchi, O.
  • Organizer: 8th Annual Meeting of the International Cytokine & Interferon Society
  • Int'l Joint Research
• [Presentation] Regulation of immune responses by RNA degradation (2019)
  • Author(s): Osamu Takeuchi
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research / Invited
• [Presentation] Control of Immune Responses via RNA Degradation (2019)
  • Author(s): Osamu Takeuchi
  • Organizer: The Polish-Japanese Meeting on RNA
  • Int'l Joint Research / Invited
• [Presentation] Unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs. (2019)
  • Author(s): Takashi Mino, Osamu Takeuchi
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Ribonucleases Regnase-1 and Regnase-3 have a critical role in cotrolling transcriptome biases in LMPP to ensure lymphopoiesis. (2019)
  • Author(s): Shinnosuke Yamada, Takuya Uehata, Osamu Takeuchi
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] ヒトにおけるコドンバイアスによるmRNA安定性制御 (2019)
  • Author(s): 竹内理
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] 免疫細胞を制御するRNA結合タンパク質の機能解析 (2019)
  • Author(s): 植畑拓也
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Endonucleases Regnase-1 and Regnase-3 regulate transcriptome biases to ensure lymphopoiesis. (2019)
  • Author(s): Takuya Uehata, Osamu Takeuchi
  • Organizer: CiRA 2019 International Symposium
  • Int'l Joint Research
• [Presentation] RNA分解による免疫細胞の制御機構 (2019)
  • Author(s): 竹内理
  • Organizer: 第8回さきがけ「RNAと生体機能」研究会
• [Presentation] Critical roles of endonucleases Regnase-1 and Regnase-3 in early lymphopoiesis. (2019)
  • Author(s): Takuya Uehata, Osamu Takeuchi
  • Organizer: 17th International Congress of Immunology
  • Int'l Joint Research
• [Presentation] 免疫細胞制御における翻訳とmRNA分解の連関 (2019)
  • Author(s): 竹内理
  • Organizer: 第92回日本生化学会大会
• [Presentation] Regnase-1による炎症性mRNA分解機構 (2019)
  • Author(s): 三野享史
  • Organizer: 第7 回CCR4-NOT研究会
• [Presentation] Codon Bias Confers Stability to mRNAs via ILF2 in Humans (2019)
  • Author(s): Hia, F., Takeuchi, O
  • Organizer: 第21回日本RNA学会年会
• [Presentation] RNA分解を介した免疫制御機構 (2019)
  • Author(s): 竹内理
  • Organizer: 第40回日本炎症・再生医学会
• [Presentation] dentification of a host RNA binding protein as a novel HIV-1 restriction factor. (2018)
  • Author(s): Yamasoba, D., Sato, K., Hotter, D., EReith, E., Koepke, L., Linsenmeyer, R., Standley, D.M., Sauter, D., Koyanagi, Y., and Takeuchi, O.
  • Organizer: Cold Spring Harbor Laboratory Meeting on Retroviruses
  • Int'l Joint Research
• [Presentation] The ribonuclease Regnase-1 maintains iron homeostasis via the destabilization of iron-regulatory transcripts. (2018)
  • Author(s): Yoshinaga, M., Mino, T., and Takeuchi, O.
  • Organizer: RNA2018
  • Int'l Joint Research
• [Presentation] The role of CyclinJ in modulating innate immune cells and inflammation. (2018)
  • Author(s): Chong, Y.K., Tartey, S, and Takeuchi, O.
  • Organizer: The 25th International Symposium on Molecular Cell Biology of Macrophages.
• [Presentation] Regnase-1による炎症性mRNA分解機構 (2018)
  • Author(s): 三野享史
  • Organizer: 第6回CCR4-NOT研究会
• [Presentation] 新規RNA分解酵素によるHIV-1感染制御機構の解明 (2018)
  • Author(s): 山岨大智，佐藤佳，小柳義夫，竹内理
  • Organizer: 第29回日本生体防御学会学術総会
• [Presentation] mRNA分解による免疫調節機構とその制御 (2018)
  • Author(s): 竹内理
  • Organizer: 日本核酸医薬学会第4回年会
  • Invited
• [Presentation] Posttranscriptional control of pro-inflammatory cytokine expression by Regnase-1 and Roquin (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: WCP2018
  • Int'l Joint Research / Invited
• [Presentation] 鉄代謝を制御する転写後調節機構の解明 (2018)
  • Author(s): 吉永正憲，三野享史，Bassik, M. C.，竹内理
  • Organizer: 第20回日本RNA学会年会
  • Invited
• [Presentation] SMG1はRegnase-1経路を介して炎症性mRNAを制御する (2018)
  • Author(s): 三野享史，岩井紀貴，赤木宏太朗，山下暁朗，竹内 理
  • Organizer: 第20回日本RNA学会年会
• [Presentation] A型肝炎ウイルスIRES依存的翻訳は肝臓特異的因子により活性化される (2018)
  • Author(s): 貞廣暁利，深尾亜喜良，小坂実央，滝沢直己，船上仁範，竹内理，Duncan, K.E.，藤原俊伸
  • Organizer: 第20回日本RNA学会年会
• [Presentation] Exploring the RNA Regulational Landscape via Codon Optimality. (2018)
  • Author(s): Hia, F.
  • Organizer: RNA Frontier Meeting 2018
• [Presentation] RNA分解酵素Regnase-1による鉄代謝制御機構 (2018)
  • Author(s): 竹内 理
  • Organizer: 第４２回日本鉄バイオサイエンス学会学術集会
  • Invited
• [Presentation] Post-transcriptional control of innate immune responses (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: Japan-Germany Immunology Workshop
  • Int'l Joint Research / Invited
• [Presentation] MALT1-mediated cleavage of N4BP1, an antiviral RNase, contributes to the viral reactivation in latently HIV-1 infected cells (2018)
  • Author(s): 山岨大智，佐藤佳，小柳義夫，竹内理
  • Organizer: 第66回ウイルス学会学術集会
• [Presentation] Innate immune Sensing and Regulation (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: 第66回ウイルス学会学術集会
  • Invited
• [Presentation] Regnase-1によるmRNA分解を介した免疫制御機構 (2018)
  • Author(s): 竹内理
  • Organizer: 第91回日本生化学会大会
  • Invited
• [Presentation] Regnase-1は鉄代謝関連のmRNAを分解することで鉄恒常性を維持する (2018)
  • Author(s): 吉永正憲，三野享史，竹内理
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] mRNA分解を介した免疫制御機構 (2018)
  • Author(s): 竹内理
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] MALT1によるN4BP1の分解は潜伏感染HIV-1の再活性化を促進する (2018)
  • Author(s): 山岨大智，佐藤佳，小柳義夫，竹内理
  • Organizer: 第32回日本エイズ学会学術集会・総会
  • Invited
• [Presentation] The role of CyclinJ as a Novel Regulator in Modulating Tumor-associated Macrophage (TAM). (2018)
  • Author(s): Chong, Y.K., and Takeuchi, O.
  • Organizer: The 47th Annual Meeting of the Japanese Society for Immunology
• [Presentation] Critical roles of endonucleases Regnase-1 and Regnase-3 in early lymphopoiesis (2018)
  • Author(s): Takuya Uehata, Shinnosuke Yamada, Masaki Miyazaki, Hiroshi Kawamoto, Osamu Takeuchi
  • Organizer: Keystone Symposia, Transcription and RNA Regulation in Inflammation and Immunity (B1)
  • Int'l Joint Research / Invited
• [Presentation] Critical Roles of an RNase N4BP1 in Anti-HIV-1 Host Defense and its Control by TCR Signaling (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: Keystone Symposia, Transcription and RNA Regulation in Inflammation and Immunity (B1)
  • Int'l Joint Research / Invited
• [Book] RNA Damage and Repair (2021)
  • Author(s): Hia F and Takeuchi O
  • Total Pages: 24
  • Publisher: Springer International Publishing
  • ISBN: 9783030765705
• [Remarks] 炎症が制御される新たなメカニズムの解明
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2021-10-19-2
• [Remarks] 代謝を通じて免疫応答を制御する新たなタンパク質の発見
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2022-04-13
• [Remarks] 肺線維症における新規治療標的候補となるRNA分解酵素Regnase-1を同定
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2020-10-14-2
• [Remarks] 宿主がHIV-1感染を抑制する新たなメカニズムの解明
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190528_1.html
• [Remarks] 炎症が制御される新たなRNA分解メカニズムを解明 －新たな免疫賦活化法の開発に道筋－
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190722_2.html
• [Remarks] ヒト細胞のコドン（遺伝暗号）に隠された暗号を解明 －ヒトコドン最適化制御による治療戦略の開発へ－
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190904_2.html
• [Patent(Industrial Property Rights)] 肺高血圧症の検査方法、肺動脈性肺高血圧症の病態モデル動物、及び肺高血圧症の予防又は治療薬 (2021)
  • Inventor(s): 竹内理、夜久愛、中岡良和
  • Industrial Property Rights Holder: 竹内理、夜久愛、中岡良和
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2021-187370
  • Filing Date: 2021
• [Patent(Industrial Property Rights)] 炎症抑制用の組成物 (2018)
  • Inventor(s): 竹内理
  • Industrial Property Rights Holder: 竹内理
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-054780
  • Filing Date: 2018