PMID- 19423639 OWN - NLM STAT- MEDLINE DCOM- 20091023 LR - 20221207 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 23 IP - 9 DP - 2009 Sep TI - LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. PG - 2898-908 LID - 10.1096/fj.09-131342 [doi] AB - The importance of post-transcriptional mechanisms for the regulation of the homoeostasis of the immune system and the response to challenge by microorganisms is becoming increasingly appreciated. We investigated the contribution of microRNAs (miRNAs) to macrophage activation induced by lipopolysaccharide (LPS). We first observed that Dicer knockout in bone marrow-derived macrophages (BMDMs) increases the LPS-induced expression of some inflammation mediators. miRNA microarray analysis in BMDMs revealed that LPS significantly induces the expression of a single miRNA, miR-155, and this induction depends on enhanced miR-155 maturation from its precursors. The single-strand RNA-binding protein KH-type splicing regulatory protein (KSRP) binds to the terminal loop of miR-155 precursors and promotes their maturation. Both inhibition of miR-155 and KSRP knockdown enhance the LPS-induced expression of select inflammation mediators, and the effect of KSRP knockdown is reverted by mature miR-155. Our studies unveil the existence of an LPS-dependent post-transcriptional regulation of miR-155 biogenesis. Once induced, miR-155 finely tunes the expression of select inflammation mediators in response to LPS. FAU - Ruggiero, Tina AU - Ruggiero T AD - RNA Technology Laboratory, Centro Biotecnologie Avanzate, Genoa, Italy. FAU - Trabucchi, Michele AU - Trabucchi M FAU - De Santa, Francesca AU - De Santa F FAU - Zupo, Simona AU - Zupo S FAU - Harfe, Brian D AU - Harfe BD FAU - McManus, Michael T AU - McManus MT FAU - Rosenfeld, M Geoff AU - Rosenfeld MG FAU - Briata, Paola AU - Briata P FAU - Gherzi, Roberto AU - Gherzi R LA - eng GR - GFP04003/TI_/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090507 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Inflammation Mediators) RN - 0 (Khsrp protein, mouse) RN - 0 (Lipopolysaccharides) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (RNA-Binding Proteins) RN - 0 (Trans-Activators) RN - EC 3.1.- (Endoribonucleases) RN - EC 3.1.26.3 (Dicer1 protein, mouse) RN - EC 3.1.26.3 (Ribonuclease III) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Animals MH - DEAD-box RNA Helicases/deficiency MH - Endoribonucleases/deficiency MH - Inflammation Mediators/metabolism MH - Lipopolysaccharides/*pharmacology MH - Macrophages/*drug effects/metabolism MH - Mice MH - MicroRNAs/*metabolism MH - RNA Processing, Post-Transcriptional MH - RNA-Binding Proteins/*metabolism MH - Ribonuclease III MH - Trans-Activators/*metabolism MH - Transcriptional Activation EDAT- 2009/05/09 09:00 MHDA- 2009/10/24 06:00 CRDT- 2009/05/09 09:00 PHST- 2009/05/09 09:00 [entrez] PHST- 2009/05/09 09:00 [pubmed] PHST- 2009/10/24 06:00 [medline] AID - fj.09-131342 [pii] AID - 10.1096/fj.09-131342 [doi] PST - ppublish SO - FASEB J. 2009 Sep;23(9):2898-908. doi: 10.1096/fj.09-131342. Epub 2009 May 7.