UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance
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UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance. / Saul, Meike J; Stein, Stefan; Grez, Manuel; Jakobsson, Per-Johan; Steinhilber, Dieter; Suess, Beatrix.
in: SCI REP-UK, Jahrgang 6, 30.08.2016, S. 31995.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance
AU - Saul, Meike J
AU - Stein, Stefan
AU - Grez, Manuel
AU - Jakobsson, Per-Johan
AU - Steinhilber, Dieter
AU - Suess, Beatrix
PY - 2016/8/30
Y1 - 2016/8/30
N2 - 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.
AB - 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.
KW - CD11b Antigen/metabolism
KW - Calgranulin B/metabolism
KW - Cell Adhesion
KW - Cell Differentiation
KW - Cell Line
KW - Cell Movement
KW - Gene Expression Regulation
KW - HeLa Cells
KW - Humans
KW - MicroRNAs/metabolism
KW - Monocytes/cytology
KW - Proteomics
KW - RNA Helicases/metabolism
KW - RNA Interference
KW - RNA-Binding Proteins/genetics
KW - Reactive Oxygen Species/metabolism
KW - Trans-Activators/metabolism
U2 - 10.1038/srep31995
DO - 10.1038/srep31995
M3 - SCORING: Journal article
C2 - 27573788
VL - 6
SP - 31995
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -