MicroRNAs in Nonalcoholic Fatty Liver Disease: Novel Biomarkers and Prognostic Tools during the Transition from Steatosis to Hepatocarcinoma

Figure 1

miRNA biogenesis and function. MiRNA genes are transcribed by an RNA polymerase II (RNA Pol II), within the nucleus, as either primary monocystronic or polycistronic transcripts (pri-miRNAs), which are 5′ capped (Cap) and 3′ polyadenylated (AAA). The first processing step (cropping) is mediated by the Drosha-DGCR8 complex (also known as the microprocessor complex) to generate a ~70 nt pre-miRNA folded into a minihairpin structure, which holds a signature motif allowing for recognition by the nuclear export factor, Exportin5 (Exp5). Once exported in the cytoplasm, the RNAse III-like nuclease, Dicer, cuts the loop end of the pre-miRNA in the second processing step (maturation), creating a ~22 nt RNA duplex. The duplex is then separated in two strands of which one is degraded, whereas the other strand is selected as the mature miRNA that is loaded into the RNA-induced silencing complex (RISC), in the final step of miRNA biogenesis. This final effector complex is composed of the core protein, Argonaute (Ago), which is required for the pairing between the miRNA and target mRNAs. Depending on the degree of complementarity with the 3′-UTR of target mRNA, the mRNA is either subject to translational repression (if partial complementarity occurs) or cleavage and degradation (if perfect complementarity occurs), with the final result of mRNA silencing [26, 127].