Abstract
MicroRNAs (miRNAs) are short noncoding RNA molecules that modulate the expression of multiple target genes at the post-transcriptional level and are implicated in a wide array of cellular and developmental processes. In hematopoietic cells, miRNA levels are dynamically regulated during lineage differentiation and also during the course of the immune response. Mouse models have provided good evidence for miRNAs being key players in the establishment of hematopoietic lineages. Furthermore, miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response to a wide range of pathogens, spontaneously emerging tumors, and autoimmune cells. Deregulation of hematopoietic-specific miRNA expression results in defects in both central and peripheral tolerance, hematopoietic malignancies, and sometimes both. Abnormal expression of miRNAs—which is implicated in inflammation—has also been found in patients with rheumatoid arthritis. These findings identify miRNAs as critical targets for immunomodulatory drug development.
Key Points
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microRNAs (miRNAs) are small noncoding RNAs that control the expression of a number of genes by post-transcriptionally modulating the expression of key targets
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miRNAs usually block protein translation or induce degradation of their target mRNAs; however, enhancement of translation of repressed transcripts has also been reported
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miRNAs display a tissue-specific pattern of expression, and their levels are dynamic during lineage differentiation of hematopoietic cells
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Mouse models developed so far provide evidence that miRNAs are not only differentially expressed in hematopoietic lineages, but also that they have a physiological role during differentiation processes
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Altered expression of some miRNAs is found in patients with rheumatoid arthritis
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miRNAs are promising targets for immunomodulatory drugs
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Tili, E., Michaille, JJ., Costinean, S. et al. MicroRNAs, the immune system and rheumatic disease. Nat Rev Rheumatol 4, 534–541 (2008). https://doi.org/10.1038/ncprheum0885
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DOI: https://doi.org/10.1038/ncprheum0885
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