Abstract
MicroRNAs are important posttranscriptional regulators of gene expression, which have been shown to fine‐tune innate immune responses downstream of pattern recognition receptor (PRR) signaling. This study identifies miR‐650 as a novel PRR‐responsive microRNA that is downregulated upon stimulation of primary human monocyte‐derived dendritic cells (MDDCs) with a variety of different microbe‐associated molecular patterns. A comprehensive target search combining in silico analysis, transcriptional profiling, and reporter assays reveals that miR‐650 regulates several well‐known interferon‐stimulated genes, including IFIT2 and MXA. In particular, downregulation of miR‐650 in influenza A infected MDDCs enhances the expression of MxA and may therefore contribute to the establishment of an antiviral state. Together these findings reveal a novel link between miR‐650 and the innate immune response in human MDDCs.
Highlights
MicroRNAs are small noncoding RNAs, ß18–22 nucleotides in length, which regulate gene expression on a posttranscriptional level by binding to the 3 untranslated region (UTR) of target mRNAs, thereby inhibiting translation and/or decreasing mRNA stability [1]
We show that miR-650 is downregulated upon pattern recognition receptor (PRR) signaling in primary human monocyte-derived dendritic cells (MDDCs) and fine-tunes the expression of a number of genes with a role in the immune response
Stimulation of PRRs downregulates miR-650 expression in human MDDCs miRNA expression profiling previously performed on human MDDCs in our lab suggested downregulation of miR-650 occurs upon MDDC stimulation
Summary
MicroRNAs (miRNAs) are small noncoding RNAs, ß18–22 nucleotides in length, which regulate gene expression on a posttranscriptional level by binding to the 3 untranslated region (UTR) of target mRNAs, thereby inhibiting translation and/or decreasing mRNA stability [1]. Binding of eukaryotic miRNAs to Recent publications have shown that miRNA expression is modulated under a variety of inflammatory conditions and is involved in the dynamic regulation of the innate immune response including its development, maturation, and function [3]. Aberrant expression of selected miRNAs can give rise to impaired innate immune function and has been observed in. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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