MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ.
MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ.
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DOI：
10.1371/journal.pone.0174381
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Jura J
中科院分区：
文献类型：
--
作者：
Lipert B;Wilamowski M;Gorecki A;Jura J
CCAAT/增强子结合蛋白β（C/EBPβ）是一种转录因子，控制着体内稳态所必需的广泛基因，包括与免疫功能、炎症、代谢和生长相关的基因。单核细胞趋化蛋白-1诱导蛋白1（MCPIP 1）也称为Regnase-1，是一种RNA酶，并且已显示降低编码炎症相关蛋白的短寿命转录物的稳定性，所述炎症相关蛋白包括IL-1β、IL-6、IL-2、IL-8、IL-12 b、IER-3、c-Rel。我们以前发现C/EBPβ转录物的半衰期受MCPIP调节。为了了解MCPIP 1下调C/EBPβ的机制，我们应用了体外切割试验，随后是内切酶报告基因试验和RNA免疫沉淀（RIP）。我们证明了MCPIP 1识别C/EBPβ mRNA的3 'UTR区域，并通过引入直接的核酸内切酶切割促进其降解。
CCAAT/enhancer-binding protein beta (C/EBPβ) is a transcription factor controlling a broad range of genes essential for homeostasis, including genes related to immune functions, inflammation, metabolism and growth. Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) also called as Regnase-1 is an RNase and has been shown to decrease the stability of short-lived transcripts coding for inflammation-related proteins, including IL-1β, IL-6, IL-2, IL-8, IL-12b, IER-3, c-Rel. We found previously that the half-life of the C/EBPβ transcript is regulated by MCPIP. To understand the mechanism driving down-regulation of C/EBPβ by MCPIP1, we applied an in vitro cleavage assay, followed by a luciferase-reporter assay and RNA immunoprecipitation (RIP). We demonstrated that MCPIP1 recognizes regions of the 3’UTR of C/EBPβ mRNA and promotes its decay by introducing direct endonucleolytic cleavage.