MCPIP1 down-regulates IL-2 expression through an ARE-independent pathway.
MCPIP1 down-regulates IL-2 expression through an ARE-independent pathway.
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MCPIP1 通过 ARE 独立途径下调 IL-2 表达
DOI：
10.1371/journal.pone.0049841
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Li M;Cao W;Liu H;Zhang W;Liu X;Cai Z;Guo J;Wang X;Hui Z;Zhang H;Wang J;Wang L
IL-2在免疫细胞，特别是T淋巴细胞的存活和增殖中起关键作用。其表达在转录和转录后水平受到精确调控。已知IL-2通过3′非翻译区（3′UTR）中的富含AU的元件（ARE）被RNA结合蛋白如三曲脯氨酸（TTP）调节，以影响mRNA的稳定性。MCPIP 1是一种新的RNase，在巨噬细胞活化过程中，可通过ARE非依赖性途径降解IL-6、IL-12和TNF-α mRNA。在这里，我们报道了MCPIP 1诱导T淋巴细胞的活化，并通过使其mRNA不稳定来负调节小鼠和人原代T淋巴细胞中IL-2基因的表达。荧光素酶报告基因检测结果表明，IL-2 3′UTR中存在一个非ARE保守元件，形成茎环结构，与MCPIP 1活性相关，RNA免疫沉淀和生物素pulldown实验进一步表明MCPIP 1可与IL-2 mRNA适度结合。总之，这些数据表明，MCPIP 1通过ARE非依赖性途径下调IL-2。
IL-2 plays a key role in the survival and proliferation of immune cells, especially T lymphocytes. Its expression is precisely regulated at transcriptional and posttranscriptional level. IL-2 is known to be regulated by RNA binding proteins, such as tristetraprolin (TTP), via an AU-rich element (ARE) in the 3′-untranslated region (3′UTR) to influence the stability of mRNA. MCPIP1, identified as a novel RNase, can degrade IL-6, IL-12 and TNF-α mRNA by an ARE-independent pathway in the activation of macrophages. Here, we reported that MCPIP1 was induced in the activation of T lymphocytes and negatively regulated IL-2 gene expression in both mouse and human primary T lymphocytes through destabilizing its mRNA. A set of Luciferase reporter assay demonstrated that a non-ARE conserved element in IL-2 3′UTR, which formed a stem-loop structure, responded to MCPIP1 activity.RNA immunoprecipitation and Biotin pulldown experiments further suggested that MCPIP1 could modestly bind to IL-2 mRNA. Taken together, these data demonstrate that MCPIP1 down-regulates IL-2 via an ARE-independent pathway.
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影响因子：
32.4
作者：
Wang L;Wildt KF;Castro E;Xiong Y;Feigenbaum L;Tessarollo L;Bosselut R
通讯作者：
Bosselut R
DOI：
10.1084/jem.20092641
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liang J;Saad Y;Lei T;Wang J;Qi D;Yang Q;Kolattukudy PE;Fu M
通讯作者：
Fu M
影响因子：
64.8
作者：
SMITH, KA;GILBRIDE, KJ;FAVATA, MF
通讯作者：
FAVATA, MF
影响因子：
4.4
作者：
Ogilvie, RL;Abelson, M;Bohjanen, PR
通讯作者：
Bohjanen, PR
影响因子：
20.1
作者：
Zhou, Limei;Azfer, Asim;Kolattukudy, Pappachan E.
通讯作者：
Kolattukudy, Pappachan E.