{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Matsui M"],"funding":["NIGMS NIH HHS"],"pagination":["10086-109"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3905862"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(22)"],"pubmed_abstract":["Although many long non-coding RNAs (lncRNAs) have been discovered, their function and their association with RNAi factors in the nucleus have remained obscure. Here, we identify RNA transcripts that overlap the cyclooxygenase-2 (COX-2) promoter and contain two adjacent binding sites for an endogenous miRNA, miR-589. We find that miR-589 binds the promoter RNA and activates COX-2 transcription. In addition to miR-589, fully complementary duplex RNAs that target the COX-2 promoter transcript activate COX-2 transcription. Activation by small RNA requires RNAi factors argonaute-2 (AGO2) and GW182, but does not require AGO2-mediated cleavage of the promoter RNA. Instead, the promoter RNA functions as a scaffold. Binding of AGO2 protein/small RNA complexes to the promoter RNA triggers gene activation. Gene looping allows interactions between the promoters of COX-2 and phospholipase A2 (PLA2G4A), an adjacent pro-inflammatory pathway gene that produces arachidonic acid, the substrate for COX-2 protein. miR-589 and fully complementary small RNAs regulate both COX-2 and PLA2G4A gene expression, revealing an unexpected connection between key steps of the eicosanoid signaling pathway. The work demonstrates the potential for RNA to coordinate locus-dependent assembly of related genes to form functional operons through cis-looping."],"journal":["Nucleic acids research"],"pubmed_title":["Promoter RNA links transcriptional regulation of inflammatory pathway genes."],"pmcid":["PMC3905862"],"funding_grant_id":["GM 73042"],"pubmed_authors":["Matsui M","Shaikh S","Manoharan M","Corey DR","Kuchimanchi S","Zhang H","Chu Y","Gagnon KT","Janowski BA"],"additional_accession":[]},"is_claimable":false,"name":"Promoter RNA links transcriptional regulation of inflammatory pathway genes.","description":"Although many long non-coding RNAs (lncRNAs) have been discovered, their function and their association with RNAi factors in the nucleus have remained obscure. Here, we identify RNA transcripts that overlap the cyclooxygenase-2 (COX-2) promoter and contain two adjacent binding sites for an endogenous miRNA, miR-589. We find that miR-589 binds the promoter RNA and activates COX-2 transcription. In addition to miR-589, fully complementary duplex RNAs that target the COX-2 promoter transcript activate COX-2 transcription. Activation by small RNA requires RNAi factors argonaute-2 (AGO2) and GW182, but does not require AGO2-mediated cleavage of the promoter RNA. Instead, the promoter RNA functions as a scaffold. Binding of AGO2 protein/small RNA complexes to the promoter RNA triggers gene activation. Gene looping allows interactions between the promoters of COX-2 and phospholipase A2 (PLA2G4A), an adjacent pro-inflammatory pathway gene that produces arachidonic acid, the substrate for COX-2 protein. miR-589 and fully complementary small RNAs regulate both COX-2 and PLA2G4A gene expression, revealing an unexpected connection between key steps of the eicosanoid signaling pathway. The work demonstrates the potential for RNA to coordinate locus-dependent assembly of related genes to form functional operons through cis-looping.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Dec","modification":"2025-04-22T19:27:14.427Z","creation":"2019-03-27T01:20:50Z"},"accession":"S-EPMC3905862","cross_references":{"pubmed":["23999091"],"doi":["10.1093/nar/gkt777"]}}