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UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance.

Saul, Meike J. and Stein, Stefan and Grez, Manuel and Jakobsson, Per-Johan and Steinhilber, Dieter and Suess, Beatrix (2016):
UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance.
6, In: Scientific reports, p. 31995, ISSN 2045-2322, [Article]

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.

Item Type: Article
Erschienen: 2016
Creators: Saul, Meike J. and Stein, Stefan and Grez, Manuel and Jakobsson, Per-Johan and Steinhilber, Dieter and Suess, Beatrix
Title: UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance.
Language: English
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.

Journal or Publication Title: Scientific reports
Volume: 6
Divisions: 10 Department of Biology
10 Department of Biology > Synthetic Genetic Circuits
Date Deposited: 06 Sep 2016 07:41
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