Post-transcriptional gene expression regulation via mRNA surveillance system

• Project/Area Number: 15H04331
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Yokohama City University
• Principal Investigator: YAMASHITA AKIO 横浜市立大学, 医学部, 准教授 (20405020)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: NMD / mRNA分解 / mRNA代謝 / 翻訳終結 / 遺伝性疾患 / がん / 遺伝子 / 転写後調節 / タンパク質翻訳 / シグナル伝達 / 統合的ストレス応答 / ナンセンス変異 / 核酸 / 生体分子 / 酵素 / 転写五兆節

Outline of Final Research Achievements

The nonsense-mediated mRNA decay (NMD) pathway it acts to selectively identify and degrade mRNAs that contain a premature translation termination codon (PTC), and hence reduce the accumulation of potentially toxic truncated proteins. SMG1, a member of the PIKK (phosphoinositide 3-kinase related kinases) family, plays a critical role in NMD. According to prevailing models, NMD begins by the assembly of the SURF (SMG1-UPF1-eRF1-eRF3) complex at the ribosome, followed by UPF1 activation by additional factors such as UPF2 and UPF3.In present study we demonstrated that the interaction between human UPF2 and eukaryotic release factor 3 (eRF3). In addition, we find that UPF2 associates with SURF and ribosomes in cells, in an UPF3-independent manner. In addition, we showed that the existence of a complex comprising SMG1, UPF1 and DHX34, with functioning as a potential scaffold for UPF1 and SMG1.

Research Products

• [Int'l Joint Research] Spanish National Research Council(スペイン)
• [Int'l Joint Research] Universityu of Berne(スイス)
• [Int'l Joint Research] Spanish National Research Council(スペイン)
• [Int'l Joint Research] University of Berne(スイス)
• [Int'l Joint Research] University of Edinburgh(英国)
• [Journal Article] Angiotensin II Type 1 Receptor-associated Protein Inhibits Angiotensin II-induced Insulin Resistance with Suppression of Oxidative Stress in Skeletal Muscle Tissue (2018)
  • Author(s): Ohki Kohji、Wakui Hiromichi、Kishio Nozomu、Azushima Kengo、Uneda Kazushi、Haku Sona、Kobayashi Ryu、Haruhara Kotaro、Kinguchi Sho、Yamaji Takahiro、Yamada Takayuki、Minegishi Shintaro、Ishigami Tomoaki、Toya Yoshiyuki、Yamashita Akio、Imajo Kento、Nakajima Atsushi、Kato Ikuma、Ohashi Kenichi、Tamura Kouichi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 2846-2846
  • DOI: 10.1038/s41598-018-21270-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory profile (2018)
  • Author(s): Haruhara Kotaro、Wakui Hiromichi、Azushima Kengo、Kurotaki Daisuke、Kawase Wataru、Uneda Kazushi、Haku Sona、Kobayashi Ryu、Ohki Kohji、Kinguchi Sho、Ohsawa Masato、Minegishi Shintaro、Ishigami Tomoaki、Matsuda Miyuki、Yamashita Akio、Nakajima Hideaki、Tamura Tomohiko、Tsuboi Nobuo、Yokoo Takashi、Tamura Kouichi
  • Journal Title: Atherosclerosis Volume: 269 Pages: 236-244
  • DOI: 10.1016/j.atherosclerosis.2018.01.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endoplasmic reticulum stress preconditioning modifies intracellular mercury content by upregulating membrane transporters (2017)
  • Author(s): Usuki Fusako、Fujimura Masatake、Yamashita Akio
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12390-12390
  • DOI: 10.1038/s41598-017-09435-3
  • Peer Reviewed / Open Access
• [Journal Article] Angiotensin II Type 1 Receptor‐Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin (2017)
  • Author(s): Uneda Kazushi、Wakui Hiromichi、Maeda Akinobu、Azushima Kengo、Kobayashi Ryu、Haku Sona、Ohki Kohji、Haruhara Kotaro、Kinguchi Sho、Matsuda Miyuki、Ohsawa Masato、Minegishi Shintaro、Ishigami Tomoaki、Toya Yoshiyuki、Atobe Yoshitoshi、Yamashita Akio、Umemura Satoshi、Tamura Kouichi
  • Journal Title: Journal of the American Heart Association Volume: 6 Issue: 8
  • DOI: 10.1161/jaha.117.006120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice (2017)
  • Author(s): Wakui H, Ohki K, Azushima K, Uneda K, Haku S, Kobayashi R, Haruhara K, Kinguchi S, Matsuda M, Ohsawa M, Maeda A, Minegishi S, Ishigami T, Toya Y, Yamashita A, Umemura S, Tamura K
  • Journal Title: International Journal of Molecular Sciences Volume: 18 Issue: 3 Pages: 676-676
  • DOI: 10.3390/ijms18030676
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Translational control of mRNAs by 3'-Untranslated region binding proteins. (2017)
  • Author(s): Yamashita A, Takeuchi O.
  • Journal Title: BMB Reports Volume: 50 Pages: 194-200
  • Peer Reviewed
• [Journal Article] SMG1 (2017)
  • Author(s): Yamashita A
  • Journal Title: Encyclopedia of Signaling Molecules 2nd edition Volume: 印刷中
  • Acknowledgement Compliant
• [Journal Article] Adipocyte-Specific Enhancement of Angiotensin II Type 1 Receptor-Associated Protein Ameliorates Diet-Induced Visceral Obesity and Insulin Resistance. (2017)
  • Author(s): Azushima K, Ohki K, Wakui H, Uneda K, Haku S, Kobayashi R, Haruhara K, Kinguchi S, Matsuda M, Maeda A, Toya Y, Yamashita A, Umemura S, Tamura K.
  • Journal Title: J Am Heart Assoc. Volume: 6 Issue: 3
  • DOI: 10.1161/jaha.116.004488
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An angiotensin II type 1 receptor binding molecule has a critical role in hypertension in a chronic kidney disease model. (2017)
  • Author(s): Kobayashi R, Wakui H, Azushima K, Uneda K, Haku S, Ohki K, Haruhara K, Kinguchi S, Matsuda M, Ohsawa M, Toya Y, Nishiyama A, Yamashita A, Tanabe K, Maeshima Y, Umemura S, Tamura K.
  • Journal Title: Kidney Int. Volume: 91 Issue: 5 Pages: 1115-1125
  • DOI: 10.1016/j.kint.2016.10.035
  • Peer Reviewed
• [Journal Article] HEK293T細胞を用いたリコンビナントタンパク質精製． (2016)
  • Author(s): 山下暁朗
  • Journal Title: 実験医学 Volume: 34 Pages: 3057-3064
• [Journal Article] The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation. (2016)
  • Author(s): Melero R, Hug N, López-Perrote A, Yamashita A, Cáceres JF, Llorca O.
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 10585-10585
  • DOI: 10.1038/ncomms10585
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex. (2016)
  • Author(s): López-Perrote A, Castaño R, Melero R, Zamarro T, Kurosawa H, Ohnishi T, Uchiyama A, Aoyagi K, Buchwald G, Kataoka N, Yamashita A, Llorca O.
  • Journal Title: Nucleic Acids Res. Volume: 44 Issue: 4 Pages: 1909-1923
  • DOI: 10.1093/nar/gkv1527
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Renal Tubule Angiotensin II Type 1 Receptor-Associated Protein Promotes Natriuresis and Inhibits Salt-Sensitive Blood Pressure Elevation. (2015)
  • Author(s): Wakui H, Uneda K, Tamura K, Ohsawa M, Azushima K, Kobayashi R, Ohki K, Dejima T, Kanaoka T, Tsurumi-Ikeya Y, Matsuda M, Haruhara K, Nishiyama A, Yabana M, Fujikawa T, Yamashita A, Umemura S.
  • Journal Title: J Am Heart Assoc. Volume: 19;4(3) Issue: 3 Pages: 1-14
  • DOI: 10.1161/jaha.114.001594
  • Peer Reviewed / Open Access
• [Journal Article] 11.mRNA 3'UTR結合タンパク質による翻訳制御 (2015)
  • Author(s): 山下暁朗，竹内 理
  • Journal Title: 細胞工学 Volume: 8 Pages: 762-765
• [Journal Article] miRNAによる標的制御 (2015)
  • Author(s): 山下暁朗
  • Journal Title: 実験医学 Volume: 20 Pages: 3244-3255
• [Presentation] PI3 kinase様タンパク質リン酸化酵素SMG1による新たな転写後制御機構の発見 (2017)
  • Author(s): 山下 暁朗, 佐藤 由典, 黒澤 瞳, 廣瀬 博子, 青柳 杏子, 永井 陽子, 大野 茂男
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] PI3 kinase様タンパク質リン酸化酵素SMG1阻害による抗腫瘍効果の解析：SMG1によるNRF2活性制御の発見 (2017)
  • Author(s): 藤川 由美子, 山下 暁朗, 大貫 哲男, 鈴木 香絵, 青柳 杏子, 黒澤 瞳, 廣瀬 博子, 永井 陽子, 上村 博司, 吉田 稔, 大野 茂男
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 新規aPKC結合タンパクp200による上皮細胞極性の調節機構 (2017)
  • Author(s): 佐々木 和教, 麹谷 典子, 廣瀬 博子, 吉濱 陽平, 高柳 亜由美, 山下 暁朗, 平野 久, 大野 茂男
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] PI3 kinase様タンパク質リン酸化酵素SMG1による転写後制御 (2016)
  • Author(s): 16.山下暁朗、佐藤由典、黒澤瞳、廣瀬博子、中村良恵、青柳杏子、武石知子、安田篤史、大野茂男
  • 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: 2016-11-30
• [Presentation] 高精度転写後制御レポーターシステムの構築と検証 (2016)
  • Author(s): 安田篤史、山下暁朗、青柳杏子、中村良恵、廣瀬博子、黒澤瞳、大野茂男
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] Highly sensitive reporter system for post-transcriptional gene expression regulation. (2016)
  • Author(s): 14.Yasuda A, Aoyagi K, Nakamura Y, Hirose H, Kurosawa H, Ohno S, Yamashita A.
  • Organizer: The 21nd Annual Meeting of the RNA Society
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Molecular mechanism of mammalian nonsense-mediated mRNA decay. (2016)
  • Author(s): Yamashita A.
  • Organizer: RNA2016 satellite-symposium 'Nascent biology and ribosome function'
  • Place of Presentation: 京都大学芝蘭会館稲森ホール（京都府京都市）
  • Int'l Joint Research
• [Presentation] 動物培養細胞を用いた感度転写後制御モニタリングシステムの構築 (2015)
  • Author(s): 山下暁朗、安田篤史、青柳杏子、中村良恵、廣瀬博子、黒澤瞳、大野茂男
  • Organizer: 第37回日本分子生物学会年会・第87回日本生化学会大会 合同大会
  • Place of Presentation: 神戸商工会議所（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 高感度転写後制御レポーター導入システムの構築と検証 (2015)
  • Author(s): 安田篤史、山下暁朗、青柳杏子、中村良恵、廣瀬博子、黒澤瞳、大野茂男
  • Organizer: 第37回日本分子生物学会年会・第87回日本生化学会大会 合同大会
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2015-12-01