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Gene expression regulation via mRNA surveillance system

Research Project

Project/Area Number 23687025
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Molecular biology
Research InstitutionYokohama City University

Principal Investigator

YAMASHITA Akio  横浜市立大学, 医学部, 講師 (20405020)

Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000)
Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2011: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsNMD / mRNA分解 / mRNA代謝 / 翻訳終結 / 遺伝性疾患 / 翻訳
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 reduce the accumulation of potentially toxic truncated proteins. SMG-1 plays a critical role in NMD. I demonstrated that phosphorylated-Upf1 recruits the SMG-5:SMG-7 complex to phospho-S1096 to induce ribosome dissociation and induce decapping mediated PTC-mRNA decay. Phospho-Upf1 also recruits SMG-6 endonuclease to phospho-T28 which might be involved in PTC-mRNA end-cleavage. Intriguingly, SMG-6 and the stalk region of the UPF1 helicase domain, along with a contribution from the SQ domain, form a interaction and we also show that this region of the UPF1 helicase domain is critical for SMG6 function and NMD. I also demonstrated that UPF2, can be transferred to UPF1 within SMG-1, inducing UPF2-dependent conformational changes required to activate UPF1 within an SMG-1:UPF1:UPF2 complex.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (41 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 19 results,  Open Access: 11 results) Presentation (16 results) (of which Invited: 1 results) Book (3 results) Remarks (2 results)

  • [Journal Article] aPKCλ maintains the integrity of the glomerular slit diaphragm through trafficking of nephrin to the cell surface.2014

    • Author(s)
      Satoh D, Hirose T, Harita Y, Daimon C, Harada T, Kurihara H, Yamashita A, Ohno S.
    • Journal Title

      J Biochem.

      Volume: 156(2) Issue: 2 Pages: 115-28

    • DOI

      10.1093/jb/mvu022

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD.2014

    • Author(s)
      Melero R, Uchiyama A, Castaño R, Kataoka N, Kurosawa H, Ohno S, Yamashita A, Llorca O.
    • Journal Title

      Structure.

      Volume: 22(8) Issue: 8 Pages: 1105-19

    • DOI

      10.1016/j.str.2014.05.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD.2014

    • Author(s)
      Nicholson P, Josi C, Kurosawa H, Yamashita A, Mühlemann O.
    • Journal Title

      Nucleic Acids Res.

      Volume: 42(14) Issue: 14 Pages: 9217-35

    • DOI

      10.1093/nar/gku645

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A hemizygous GYG2 mutation and Leigh syndrome: a possible link?2014

    • Author(s)
      Imagawa E, Osaka H, Yamashita A, Shiina M, Takahashi E, Sugie H, Nakashima M, Tsurusaki Y, Saitsu H, Ogata K, Matsumoto N, Miyake N.
    • Journal Title

      Hum Genet.

      Volume: 133(2 Issue: 2 Pages: 225-34

    • DOI

      10.1007/s00439-013-1372-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity.2013

    • Author(s)
      Maeda A, Tamura K, Wakui H, Dejima T, Ohsawa M, Azushima K, Kanaoka T, Uneda K, Matsuda M, Yamashita A, Miyazaki N, Yatsu K, Hirawa N, Toya Y, Umemura S.
    • Journal Title

      J Am Heart Assoc.

      Volume: 2(4) Issue: 4

    • DOI

      10.1161/jaha.113.000312

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endoplasmic reticulum stress preconditioning attenuates methylmercury-induced cellular damage by inducing favorable stress responses.2013

    • Author(s)
      Usuki F, Fujimura M, Yamashita A
    • Journal Title

      Sci Rep

      Volume: 3 Issue: 1 Pages: 2346-2346

    • DOI

      10.1038/srep02346

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An epigenetic switch is crucial for spermatogonia to exit the undifferentiated state toward a Kit-positive identity2013

    • Author(s)
      Shirakawa, T., Yaman-Deveci, R., Tomizawa, S., Kamizato, Y., Nakajima, K., Sone, H., Sato, Y., Sharif, J., Yamashita, A., Takada-Horisawa, Y., Yoshida, S., Ura, K., Muto, M., Koseki, H., Suda, T., and Ohbo, K.
    • Journal Title

      Development

      Volume: 140 Issue: 17 Pages: 3565-3576

    • DOI

      10.1242/dev.094045

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of SMG-8, a subunit of SMG-1 kinase, ameliorates nonsense-mediated mRNA decay-exacerbated mutant phenotypes without cytotoxicity.2013

    • Author(s)
      Usuki F, Yamashita A, Shiraishi T, Shiga A, Onodera O, Higuchi I, Ohno S
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 110 Issue: 37 Pages: 15037-42

    • DOI

      10.1073/pnas.1300654110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The novel PAR-1-binding protein MTCL1 has crucial roles in organizing microtubules in polarizing epithelial cells.2013

    • Author(s)
      Sato Y, Akitsu M, Amano Y, Yamashita K, Ide M, Shimada K, Yamashita A, Hirano H, Arakawa N, Maki T, Hayashi I, Ohno S, Suzuki A.
    • Journal Title

      J Cell Sci.

      Volume: 126(Pt 20) Pages: 4671-83

    • DOI

      10.1242/jcs.127845

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity.2013

    • Author(s)
      Azushima K, Tamura K, Wakui H, Maeda A, Ohsawa M, Uneda K, Kobayashi R, Kanaoka T, Dejima T, Fujikawa T, Yamashita A, Toya Y, Umemura S.
    • Journal Title

      PLoS One.

      Volume: 8(10) Issue: 10 Pages: e75560-e75560

    • DOI

      10.1371/journal.pone.0075560

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension.2013

    • Author(s)
      Wakui H, Dejima T, Tamura K, Uneda K, Azuma K, Maeda A, Ohsawa M, Kanaoka T, Azushima K, Kobayashi R, Matsuda M, Yamashita A, Umemura S.
    • Journal Title

      Cardiovasc Res.

      Volume: 100(3) Issue: 3 Pages: 511-9

    • DOI

      10.1093/cvr/cvt225

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonsense-mediated mRNA decay - Mechanisms of substrate mRNA recognition and degradation in mammalian cells.2013

    • Author(s)
      Schweingruber, C.
    • Journal Title

      Biochim Biophys Acta.

      Volume: Epub ahead of print Issue: 6-7 Pages: 1-11

    • DOI

      10.1016/j.bbagrm.2013.02.005

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay.2013

    • Author(s)
      Yamashita A.
    • Journal Title

      Genes Cells.

      Volume: 18(3) Issue: 3 Pages: 161-75

    • DOI

      10.1111/gtc.12033

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Physiology and Pathophysiology of a Novel Angiotensin Receptor-binding Protein ATRAP/Agtrap.2013

    • Author(s)
      Tamura, K.
    • Journal Title

      Curr Pharm Des.

      Volume: 19 Pages: 3043-3048

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Analysis of interferon-beta mRNA stability control after poly(I:C) stimulation using RNA metabolic labeling by ethynyluridine.2012

    • Author(s)
      Abe K, Ishigami T, Shyu A. B, Ohno S, Umemura S, Yamashita A
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 428(1) Issue: 1 Pages: 44-49

    • DOI

      10.1016/j.bbrc.2012.09.144

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heat shock protein 90 regulates phosphatidylinositol 3-kinase-related protein kinase family proteins together with the RUVBL1/2 and Tel2-containing co-factor complex2012

    • Author(s)
      Izumi N, Yamashita A, Hirano H, Ohno S
    • Journal Title

      Cancer Sci

      Volume: 103 Issue: 1 Pages: 50-57

    • DOI

      10.1111/j.1349-7006.2011.02112.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD2012

    • Author(s)
      Okada-Katsuhata Y, Yamashita A, Kutsuzawa K, Izumi N, Hirahara F, Ohno S
    • Journal Title

      Nucleic Acids Res

      Volume: 40 Issue: 3 Pages: 1251-1266

    • DOI

      10.1093/nar/gkr791

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL22012

    • Author(s)
      Izumi N, Yamashita A and Ohno S
    • Journal Title

      Nucleus

      Volume: 3 Issue: 1 Pages: 29-43

    • DOI

      10.4161/nucl.18926

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel role for hSMG-1 in stress granule formation.2011

    • Author(s)
      Brown JA. et al.
    • Journal Title

      Cancer Sci.

      Volume: 31 Issue: 22 Pages: 4417-4429

    • DOI

      10.1128/mcb.05987-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy.2011

    • Author(s)
      Saitsu H. et al.
    • Journal Title

      Am J Hum Genet.

      Volume: 89 Issue: 5 Pages: 644-651

    • DOI

      10.1016/j.ajhg.2011.10.003

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] RNA品質管理機構を介した遺伝子発現制御.2015

    • Author(s)
      山下 暁朗
    • Organizer
      野本明男先生追悼記念シンポジウム
    • Place of Presentation
      ラフォーレ修善寺(静岡県伊東市)
    • Year and Date
      2015-01-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 異常終止コドン依存的mRNA分解機構におけるSMG-1とUPF1の活性制御機構.2014

    • Author(s)
      山下 暁朗, 内山 晃子, 黒澤 瞳, 中村 良恵, 青柳 杏子, 片岡 直行, 大野 茂男
    • Organizer
      第37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
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] mRNA監視機構分子機構解析とその応用.2014

    • Author(s)
      山下 暁朗
    • Organizer
      「RNAと生体機能」第3回懇話会
    • Place of Presentation
      ラフォーレ伊藤(静岡県伊東市)
    • Year and Date
      2014-10-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] p50 stabilizes the cell surface E-cadherin and regulates development and maturation of tight Junctions through the PAR complex.2013

    • Author(s)
      Fujikawa Y, Harita Y, Hirose T, Yamashita A, Sasaki K, Hirano H, Ohno S
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2013-12-05
    • Related Report
      2013 Annual Research Report
  • [Presentation] Formation of mRNA surveillance complex during aberrant termination recognition.2013

    • Author(s)
      Yamashtia A, Uchiyama A, Kataoka N, Kurosawa H, Nakamura Y, Ohno S
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2013-12-04
    • Related Report
      2013 Annual Research Report
  • [Presentation] An efficient affinity purification method for interaction proteomics in mammalian cells.2013

    • Author(s)
      Yamashita A, Kurosawa H, Hirano H, Ohno S
    • Organizer
      HUPO 12th Annual World Congress
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2013-09-16
    • Related Report
      2013 Annual Research Report
  • [Presentation] 動物細胞におけるmRNA監視機構の分子機構の研究2011

    • Author(s)
      山下暁朗
    • Organizer
      第34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)(招待講演)
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] The role of SMG-1 in nonsense-mediated mRNA decay2011

    • Author(s)
      Yamashita A
    • Organizer
      RNA Asia Studies
    • Place of Presentation
      Fullon Hot Spring Kesort at Tamsui (Taiwan)
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] The SMG-1 mediated N- and C-terminal phosphorylation of Upf1 create binding platform of SMG-6 and the SMG5:SMG-7 complex during nonsense-mediated mRNA decay2011

    • Author(s)
      Yamashita A, Okada-Katsuhata Y, Kutsuzawa K, Izumi N, Hirahara F, Ohno S
    • Organizer
      第16回国際RNA学会年会
    • Place of Presentation
      京都国際会館(京都府)
    • Year and Date
      2011-06-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] PIKKファミリーキナーゼSMG-1の活性制御とmRNA監視機構

    • Author(s)
      山下暁朗
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Transcriptional Timing Determines the Stability of Interferon-beta (IFN-β) mRNA

    • Author(s)
      安部開人
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] mRNA surveillance approaches clinic.

    • Author(s)
      山下暁朗
    • Organizer
      第14回日本RNA学会年会
    • Place of Presentation
      川内萩ホール(宮城県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] mRNA surveillance approaches clinic.

    • Author(s)
      山下暁朗
    • Organizer
      第12回蛋白質科学学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Translation timings determine the density of interferon-beta mRNA stability

    • Author(s)
      安部開人
    • Organizer
      The 22nd CDB meeting -RNA
    • Place of Presentation
      理化学研究所発生再生科学総合研究センター(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Specific inhibition of SMG-8 rescues effectively the mutant phenotypes exacerbated by nonsensemediated mRNA decay.

    • Author(s)
      Yamashita, A.
    • Organizer
      RNA and Biofunctions Meeting
    • Place of Presentation
      ホテルレオパレス博多(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Specific inhibition of SMG-8 rescues effectively the mutant phenotypes exacerbated by nonsensemediated mRNA decay.

    • Author(s)
      Yamashita, A.
    • Organizer
      CSHL meeting 2012 transnational control
    • Place of Presentation
      Cold Spring Harbor, USA
    • Related Report
      2012 Annual Research Report
  • [Book] 実験医学 vol.30 No.92013

    • Author(s)
      山下暁朗
    • Total Pages
      10
    • Publisher
      mRNA品質管理機構の最新理解と新たな標的治療の可能性
    • Related Report
      2012 Annual Research Report
  • [Book] 横浜医学2012年1月63巻1号2012

    • Author(s)
      山下暁朗
    • Total Pages
      16
    • Publisher
      横浜市立大学医学会
    • Related Report
      2011 Annual Research Report
  • [Book] 臨床検査2011年9月55巻9号2011

    • Author(s)
      山下暁朗
    • Total Pages
      6
    • Publisher
      医学書院
    • Related Report
      2011 Annual Research Report
  • [Remarks] 大野研究室 分子細胞生物学 Cell Signaling

    • URL

      http://www-user.yokohama-cu.ac.jp/~ohnos/Japanease/indexJ.html

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
  • [Remarks]

    • URL

      http://www-user.yokohama-cu.ac.jp/~ohnos/Japanease/indexJ.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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