tailieunhanh - Báo cáo khoa học: Interleukin-1-inducible MCPIP protein has structural and functional properties of RNase and participates in degradation of IL-1b mRNA

In human monocyte-derived macrophages, the MCPIPgene (monocyte chemoattractant protein-induced protein) is strongly activated by inter-leukin-1b(IL-1b). Using bioinformatics, a PIN domain was identified, span-ning amino acids 130-280; such domains are known to possess structural features of RNases. Recently, RNase properties of MCPIP were confirmed on transcripts coding for interleukins IL-6 and IL-12p40. | ễFEBS Journal Interleukin-1-inducible MCPIP protein has structural and functional properties of RNase and participates in degradation of IL-1 b mRNA Danuta Mizgalska1 Paulina Wegrzyn1 Krzysztof Murzyn2 Aneta Kasza1 Aleksander Koj1 Jacek Jura3 Barbara Jarzab4 and Jolanta Jura1 1 Department of CellBiochemistry Jagiellonian University Krakow Poland 2 Department of Biophysics Jagiellonian University Krakow Poland 3 NationalResearch Institute of AnimalProduction Balice Poland 4 M. Sklodowska-Curie MemorialInstitute Gliwice Poland Keywords IL-1P transcript degradation inflammation MCPIP PIN domain RNase Correspondence J. Jura Department of CellBiochemistry Faculty of Biochemistry Biophysics and Biotechnology 7 Gronostajowa Street 30-387 Krakow Poland Fax 48 12 664 6902 Tel 48 12 664 6359 E-mail Received 28 April2009 revised 23 September 2009 accepted 20 October 2009 doi In human monocyte-derived macrophages the MCPIP gene monocyte chemoattractant protein-induced protein is strongly activated by interleukin-1 b IL-1P . Using bioinformatics a PIN domain was identified spanning amino acids 130-280 such domains are known to possess structural features of RNases. Recently RNase properties of MCPIP were confirmed on transcripts coding for interleukins IL-6 and IL-12p40. Here we present evidence that siRNA-mediated inhibition of the MCPIP gene expression increases the level of the IL-1P transcript in cells stimulated with LPS whereas overexpression of MCPIP exerts opposite effects. Cells with an increased level of wild-type MCPIP showed lower levels of IL-1P mRNA. However this was not observed when mutant forms of MCPIP either entirely lacking the PIN domain or with point mutations in this domain were used. The results of experiments with actinomycin D indicate that lower levels of IL-1P mRNA are due to shortening of the IL-1P transcript half-life and are not related to the presence of AU-rich elements in the 3 UTR. The .