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

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 m
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.
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Metadaten
Author:Meike J. Saul, Stefan Stein, Manuel Grez, Per-Johan Jakobsson, Dieter Steinhilber, Beatrix Süß
URN:urn:nbn:de:hebis:30:3-465665
DOI:http://dx.doi.org/10.1038/srep31995
ISSN:2045-2322
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=27573788
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2016
Date of first Publication:2016/08/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/06/05
Tag:Myelopoiesis; miRNA in immune cells
Volume:6
Issue:Art. 31995
Pagenumber:11
First Page:1
Last Page:11
Note:
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
HeBIS PPN:433816392
Institutes:Pharmazie
Georg-Speyer-Haus
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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