MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ.
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.
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Krakow, Poland.
Barbara
B
Lipert
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Krakow, Poland.
Mateusz
M
Wilamowski
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Physical Biochemistry, Krakow, Poland.
Andrzej
A
Gorecki
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Krakow, Poland.
Jolanta
J
Jura
D020413:3' Untranslated Regions / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; C099815:IER3 protein, human; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D014157:Transcription Factors; D018664:Interleukin-12; D012260:Ribonucleases; C510646:ZC3H12A protein, human