Mechanistic insight into miRNA function
Originally, miRNAs derive from transcripts that are subsequently processed by the enzyme complexes Drosha and Dicer into mature forms of about 22 nucleotides. These are then loaded onto the RNA-induced silencing complex (RISC) to mediate degradation and/or translation inhibition of specific target mRNAs. Accumulating evidence indicates that the terminal loop structure of miRNA precursors is central for miRNA processing co-activators such as KSRP, and co-repressors such as Lin28. KSRP additionally serves as an essential maturation factor of miR-155 in activated macrophages. miR-155 regulates both adaptive and innate immune responses and in macrophages, miR-155 maturation is induced upon lipopolysaccharide stimulus. Scientists on the EU-funded MIR155 (microRNA-155 expression control and function in innate immune inflammatory response) project set out to delineate the process of KSRP-mediated miR-155 maturation. In this context, they followed a proteomic approach and discovered novel proteins associated with KSRP. Project researchers generated a miR-155 knockout mouse model to investigate the regulation of the direct miR-155-target mRNAs and the impact of the KSRP-partners on the activity of miR-155 in macrophages. Results point towards novel mechanisms of KSRP/miRNA-mediated regulation of gene expression in activated macrophages that could affect the overall inflammatory response. Taken together, the study provided fundamental insight into the process of miRNA biogenesis and underscored the regulatory role of these molecules in immune function. Importantly, MIR155 findings contribute towards the delineation of the very complex network of gene expression regulation.
Keywords
MiRNA, KSRP, miR-155, macrophage, immune response
