MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ
نویسندگان
چکیده
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.
منابع مشابه
Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation
Regnase-1 (also known as Zc3h12a and MCPIP1) is an RNase that destabilizes a set of mRNAs, including Il6 and Il12b, through cleavage of their 3' UTRs. Although Regnase-1 inactivation leads to development of an autoimmune disease characterized by T cell activation and hyperimmunoglobulinemia in mice, the mechanism of Regnase-1-mediated immune regulation has remained unclear. We show that Regnase...
متن کاملMCPIP1 suppresses hepatitis C virus replication and negatively regulates virus-induced proinflammatory cytokine responses.
Human MCP-1-induced protein 1 (MCPIP1, also known as ZC3H12A and Regnase-1) plays important roles in negatively regulating the cellular inflammatory response. Recently, we found that as an RNase, MCPIP1 has broad-spectrum antiviral effects by targeting viral RNA. In this study, we demonstrated that MCPIP1 expression was induced by hepatitis C virus (HCV) infection in Huh7.5 hepatoma cells. MCPI...
متن کاملRegnase-1 and Roquin regulate inflammatory mRNAs
Inflammation is mediated by proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6). Innate immune cells sense pathogen infection via Toll-like receptors (TLRs) and rapidly induced production of cytokines. The expression of cytokine genes is tightly regulated at both transcriptional and post-transcriptional levels. Whereas transcription is the first step in the re...
متن کاملRegnase-1 and Roquin Regulate a Common Element in Inflammatory mRNAs by Spatiotemporally Distinct Mechanisms
Regnase-1 and Roquin are RNA binding proteins essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. However, their mechanistic relationship has yet to be clarified. Here, we show that, although Regnase-1 and Roquin regulate an overlapping set of mRNAs via a common stem-loop structure, they function in distinct subcellular locations: ribosome/endoplasmic ...
متن کاملCombinatorial Recruitment of CREB, C/EBPβ and c-Jun Determines Activation of Promoters upon Keratinocyte Differentiation
BACKGROUND Transcription factors CREB, C/EBPβ and Jun regulate genes involved in keratinocyte proliferation and differentiation. We questioned if specific combinations of CREB, C/EBPβ and c-Jun bound to promoters correlate with RNA polymerase II binding, mRNA transcript levels and methylation of promoters in proliferating and differentiating keratinocytes. RESULTS Induction of mRNA and RNA po...
متن کامل