MicroRNAs of the immune system: roles in inflammation and cancer

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary target mRNAs and either promoting their decay or inhibiting their translation. Most eukaryotic genomes studied encode miRNAs, which are processed from longer noncoding transcripts through pathways conserved from fungi to plants to animals. miRNAs are now understood to be key mediators of developmental transitions in a number of model organisms. With respect to the immune system, miRNAs affect all facets of immune system development, from hematopoiesis to activation in response to infection during both the innate and the adaptive immune response. At the same time, miRNA dysregulation is a central event in the development and pathophysiology of a number of cancers of the immune system. Here we will discuss our current understanding of this general regulatory mechanism, focusing on its involvement in inflammation and in oncogenesis.

Figures

Figure 1. Biosynthesis of microRNA

Primary-microRNA (pri-miRNA) transcription takes place in the nucleus by RNA polymerase II. Pri-miRNA is then processed in the nucleus by microprocessor complex composed of Drosha and DCGR8, producing a precursor-miRNA which is then exported out of the nucleus by Exportin-5 and Ran-GTP. In the cytoplasm, further processing by Dicer and TRPB releases a miRNA duplex. One strand is degraded while the mature miRNA is incorporated into the RNA-induced silencing complex (RISC), which leads to targeting to an mRNA leading to its destabilization or repression of translation.

Figure 2. Involvement of miRNAs in B-cell Differentiation

MicroRNAs are involved in B-cell differentiation and maturation. MicroRNAs near the arrows have been shown to be involved in that developmental stage, by affecting (downregulation-red arrows or indirectly stimulating-green arrows) the labeled factors (black) involved in that developmental transition.