miRNAs are short segment of RNAs that fold into a double-stranded structure, and, following enzymatic processing, suppress the gene expression via a complementarity-based target RNA recognition. miRNAs are naturally present in animals and plants. Mature duplexes are 18-25 nucleotides long. Mature miRNAs are structurally similar to siRNAs produced from exogenous dsRNA, but before reaching maturity, miRNAs must first undergo extensive post-transcriptional modification. A miRNA is expressed from a much longer RNA-coding gene as a primary transcript known as a pri-miRNA which is processed, in the cell nucleus, to a 70-nucleotide stem-loop structure called a pre-miRNA by the complex consisting of an RNase III enzyme called Drosha and a dsRNA-binding protein DGCR8. The dsRNA portion of the pre-miRNA is bound and cleaved by Dicer to produce the mature miRNA molecule that can be integrated into the RISC complex. [i]
Differently from siRNA, a miRNA-loaded RISC complex scans cytoplasmic mRNAs for potential complementarity. Instead of destructive cleavage, miRNAs target the 3′ untranslated region (UTR) regions of mRNAs where they typically bind with imperfect complementarity, thus blocking the access of ribosomes for translation[ii].
[i] Gregory RI, Chendrimada TP, Shiekhattar R (2006). “MicroRNA biogenesis: isolation and characterization of the microprocessor complex”. MicroRNA Protocols. Methods in Molecular Biology. 342. pp. 33–47. doi:10.1385/1-59745-123-1:33. ISBN 978-1-59745-123-9. PMID 16957365.
[ii] Roberts, TC (2015). “The microRNA Machinery”. MicroRNA: Basic Science. Advances in Experimental Medicine and Biology. 887. pp. 15–30. doi:10.1007/978-3-319-22380-3_2. ISBN 978-3-319-22379-7. PMID 26662984.