Fig. 1

The process of creating and using miRNAs involves several steps. It starts with producing a pri-miRNA, which is then cut by the microprocessor complex made up of Drosha and DGCR8. This forms a pre-miRNA, which is moved to the cytoplasm and turned into a mature miRNA duplex. One of the strands is then loaded onto an Argonaute protein to make a miRISC. Non-canonical pathways may also be used, where small hairpin RNAs are cut by the microprocessor complex and sent to the cytoplasm for further processing. These can be cleaved by AGO2 without Dicer’s involvement. Mirtrons and m7G-pre-miRNAs have distinct processes for maturation in the cytoplasm, with mirtrons utilizing Exportin5/RanGTP and m7G-pre-miRNAs using Exportin1. However, both pathways result in the formation of a functional miRISC complex, which hinders translation by disrupting the eIF4F complex. Additionally, GW182 proteins recruit PAN2/3 and CCR4-NOT to cause deadenylation of the target mRNA. The remaining m7G cap is removed by the decapping complex, allowing for degradation by XRN1