國家衛生研究院 NHRI:Item 3990099045/13493
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13493


    Title: Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
    Authors: Lin, CC;Shen, YR;Chang, CC;Guo, XY;Young, YY;Lai, TY;Yu, IS;Lee, CY;Chuang, TH;Tsai, HY;Hsu, LC
    Contributors: Immunology Research Center
    Abstract: Different levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3' ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by Zc3h12a gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on Zc3h12a 3'-UTR, thereby promotes Zc3h12a uridylation and degradation. Zc3h12a from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated Zc3h12a is significantly reduced in Tut7(-/-) cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators.
    Date: 2021-06-29
    Relation: Nature Communications. 2021 Jun 29;12:Article number 3878.
    Link to: http://dx.doi.org/10.1038/s41467-021-24177-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000671746900001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85108976380
    Appears in Collections:[Tsung-Hsien Chuang] Periodical Articles

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