microRNA 生合成変動が引き起こす病態生理現象  [in Japanese] Pathophysiological events induced by alteration of microRNA biogenesis pathway.  [in Japanese]

Access this Article

Author(s)

    • 戸高 寛 TODAKA Hiroshi
    • 高知大学医学部生理学講座循環制御学|高知大学総合研究センター分子生物学教室 Department of Cardiovascular Control, Kochi Medical School|Laboratory of Molecular Biology, Sience Research Center, Kochi Medical School
    • 樋口 琢磨 HIGUCHI Takuma
    • 高知大学総合研究センター分子生物学教室 Laboratory of Molecular Biology, Sience Research Center, Kochi Medical School
    • 坂本 修士 SAKAMOTO Shuji
    • 高知大学総合研究センター分子生物学教室 Laboratory of Molecular Biology, Sience Research Center, Kochi Medical School

Abstract

<p>microRNA(miRNA)は,標的となるメッセンジャーRNAの翻訳を阻害することで様々な生命現象を制御する。これらのmiRNAの生合成は,多くのRNA結合タンパク質により厳密に制御されている。従ってmiRNA生合成を制御するRNA結合タンパク質の異常な発現変動は生体システムの破綻を引き起こし,疾患発症に影響を及ぼすことが知られている。我々は,これまでに,過剰発現したRNA結合タンパク質Nuclear Factor 90(NF90)-NF45複合体がmiRNA初期転写産物のプロセシングを抑制し,miRNA産生を負に制御することを見出している。本稿では,NF90-NF45過剰発現マウスを用いた表現型解析および機能解析より見出された「過剰発現したNF90-NF45はmiR-133生合成を抑制し,骨格筋の中心核化および筋委縮を誘導する」ことを主として紹介する。加えて,近年発表した「肝細胞癌において発現増加するNF90-NF45がmiR-7生合成機構を抑制して細胞増殖を促進する」ことついても紹介する。これらの知見を通じてNF90-NF45の過剰発現および発現増加が及ぼすmiRNA生合成機構の制御とその機構を介した疾患発症について述べる。</p>

<p>MicroRNAs (miRNAs), which are 21-25 nucleotides in length, regulate various developmental and cellular processes through translational inhibition of target messenger RNA in vertebrates. The biogenesis of miRNAs is strictly controlled by numerous RNA binding proteins (RBPs). Therefore, alteration in expression or RNA binding activity of the RBPs induces a number of diseases by aberrant generation of miRNAs. We previously demonstrated that overexpression of nuclear factor 90 (NF90)-NF45 complex suppresses primary-miRNA processing step, resulting in a reduction of mature miRNA production <i>in vitro</i>. In this review, we mainly presented the data obtained from phenotypic analysis of transgenic mice overexpressing NF90-NF45 (NF90-NF45 Tg mice). NF90-NF45 Tg mice exhibited skeletal muscle atrophy accompanied with centronuclear muscle fibers. Finally, we found that this centronuclear myopathy is induced by a rise in dynamin 2, a causative gene of the myopathy and a target of miR-133, through an NF90-NF45-induced inhibition of miR-133 biogenesis. In addition to this observation, we also examined whether the phenomenon that overexpression of NF90-NF45 negatively regulates the miRNA biogenesis pathway involves in the occurrence of human diseases. As a result, the high expression of NF90-NF45 was found to accelerate cell proliferation by activation of epidermal growth factor receptor (EGFR)-dependent Akt signaling via an NF90-NF45-induced suppression of miR-7, which is targeted to EGFR, in hepatocellular carcinoma. Taken together, it was revealed that overexpression of NF90-NF45 influences pathophysiological events including myopathy and cancer through its ability to regulate the miRNA biogenesis pathway.</p>

Journal

  • Hikaku seiri seikagaku(Comparative Physiology and Biochemistry)

    Hikaku seiri seikagaku(Comparative Physiology and Biochemistry) 33(4), 183-190, 2016

    THE JAPANESE SOCIETY FOR COMPARATIVE PHYSIOLOGY AND BIOCHEMISTRY

Codes

  • NII Article ID (NAID)
    130005286662
  • NII NACSIS-CAT ID (NCID)
    AN10391932
  • Text Lang
    JPN
  • ISSN
    0916-3786
  • NDL Article ID
    027837891
  • NDL Call No.
    Z18-1651
  • Data Source
    NDL  J-STAGE 
Page Top