title: UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance.
abstract: UPF1 is a key player in nonsense mediated mRNA decay (NMD) but also involved in posttranscriptional gene regulation. In this study we found that UPF1 regulates the expression of genes with functions in inflammation and myeloid cell differentiation via hnRNP E2. The majority of the UPF1-regulated genes identified in monocytic cells contain a binding site for hnRNP E2 within 5' UTR located introns with hnRNP E2 acting here as splicing regulator. We found that miRNA-328 which is significantly induced during monocytic cell differentiation acts independently from its gene silencing function as RNA decoy for hnRNP E2. One representative gene controlled by the hnRNP E2/miRNA-328 balance is S100A9 which plays an important role in cell differentiation and oxidative stress response of monocytes. Induction of miRNA-328 expression during cell differentiation antagonizes the blockade by hnRNP E2 which results in the upregulation of CD11b expression and ROS production in monocytic cells. Taken together, our data indicate that upregulation of miR-328 is responsible for the induction of hnRNP E2 target genes during myeloid cell differentiation.
authors: Department of Biology, Technical University Darmstadt, Schnittspahnstr. 10, 64287 Darmstadt, Germany.|Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt/M., Germany.
authors: Meike J
authors: MJ
authors: Saul
authors: Stefan
authors: S
authors: Stein
authors: Manuel
authors: M
authors: Grez
authors: Department of Medicine, Rheumatology unit, Karolinska Institute, 17176 Stockholm, Sweden.
authors: Per-Johan
authors: PJ
authors: Jakobsson
authors: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt/M., Germany.
authors: Dieter
authors: D
authors: Steinhilber
authors: Department of Biology, Technical University Darmstadt, Schnittspahnstr. 10, 64287 Darmstadt, Germany.
authors: Beatrix
authors: B
authors: Suess
mesh_terms: D039481:CD11b Antigen / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D040901:Proteomics; D020365:RNA Helicases / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D040502:Calgranulin B; C509295:ITGAM protein, human; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; C501903:PCBP2 protein, human; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human