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Wig1 plays a critical role in microRNA mediated mRNA decay through control of RISC recruitment 원문보기

  • 저자

    이형철

  • 학위수여기관

    Graduate School, Korea University

  • 학위구분

    국내박사

  • 학과

    生命科學科 細胞生物學專攻

  • 지도교수

    高永圭

  • 발행년도

    2014

  • 총페이지

    xix, 119장

  • 키워드

    senescence RNA binding protein Wig1 microRNA;

  • 언어

    eng

  • 원문 URL

    http://www.riss.kr/link?id=T13541985&outLink=K  

  • 초록

    RNA-binding proteins (RBPs) involving in mRNA turnover, transport, translation, and stability play a critical role for the regulation of gene expression in response to various signals and stresses. Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Wig1 that is identified as an ionizing radiation (IR)-responsive RBP from the microarray analysis of IR-induced premature senescence, plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence. Also, acyl-CoA thioesterase 7 (ACOT7) mRNA was identified as a Wig1 target. ACOT7 mRNAs were upregulated and downregulated in Wig1-depleted and -overexpressed cells. It was confirmed that cell cycle progression was regulated through control of ACOT7. Together, these data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA-mediated gene silencing. In addition, these findings indicate that fine tuning of target mRNA levels by Wig1 is essential for the prevention of cellular senescence and cell cycle arrest.


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