Abstract
MicroRNAs (miRNAs) play a key role in fine-tuning host immune homeostasis and responses through the negative regulation of mRNA stability and translation. The pathways regulated by miRNAs are well characterized, but the precise mechanisms that control the miRNA-mediated regulation of gene expression during immune cell-development and immune responses to invading pathogens are incompletely understood. Context-specific interactions of miRNAs with other RNA species or proteins may modulate the function of a given miRNA. Dysregulation of miRNA function is associated with various human diseases, such as cardiovascular diseases and cancers. Here, we review the potential modulators of miRNA function in the immune system, including the transcription regulators of miRNA genes, miRNA-processing enzymes, factors affecting miRNA targeting, and intercellular communication.
Highlights
The development and function of immune cells are vital for host defense against external and internal threats and for immune resolution following the elimination of threats, which requires rapid changes in the transcriptome and proteome
One strand of the miRNA duplex is usually incorporated into the miRNA-induced silencing complexes through the Argonaut (Ago) proteins, which guide the binding of miRNAs to complementary sites mainly located in the 3 untranslated regions (3 UTRs) of the target mRNAs [10,11]. miRNAs are estimated to control 30%–80% of mammalian genes by repressing translation and reducing the stability of target mRNAs [12,13,14]
In contrast to the in vitro study, Ksrp deficient mice displayed a reduced inflammatory response, characterized by a reduction in C-X-C motif chemokine ligand 1 (CXCL1), inducible nitric oxide synthase and tumor necrosis factor (TNF), and a reduced infiltration of monocytes and neutrophils using the model of inflammatory arthritis [104], implicating the complicated network regulated by KH-type splicing regulatory protein (KSRP) in the immune system
Summary
The development and function of immune cells are vital for host defense against external and internal threats and for immune resolution following the elimination of threats, which requires rapid changes in the transcriptome and proteome. These changes are tightly regulated at both the transcriptional and post-transcriptional levels, where microRNAs (miRNAs) have been demonstrated to be crucial molecular players. This review summarizes our initial knowledge of the mechanisms applied by the immune cells to accurately outline miRNA function, including the recruitment of transcription factors, the modification of enzymes involved in miRNA biogenesis, changes in the variants of miRNA target sites, and the uptake of exogenous miRNAs
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