Lipert Barbara, Wilamowski Mateusz, Gorecki Andrzej, Jura Jolanta
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Krakow, Poland.
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Physical Biochemistry, Krakow, Poland.
PLoS One. 2017 Mar 22;12(3):e0174381. doi: 10.1371/journal.pone.0174381. eCollection 2017.
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.
CCAAT/增强子结合蛋白β（C/EBPβ）是一种转录因子，可调控一系列对体内平衡至关重要的基因，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（MCPIP1）也称为Regnase-1，是一种核糖核酸酶，已被证明可降低编码炎症相关蛋白（包括IL-1β、IL-6、IL-2、IL-8、IL-12b、IER-3、c-Rel）的短寿命转录本的稳定性。我们之前发现C/EBPβ转录本的半衰期受MCPIP调控。为了了解MCPIP1驱动C/EBPβ下调的机制，我们进行了体外切割试验，随后进行荧光素酶报告试验和RNA免疫沉淀（RIP）。我们证明MCPIP1识别C/EBPβ mRNA 3'UTR的区域，并通过直接引入核酸内切酶切割来促进其降解。
