RNA Interference and Its Applications

Abstract

RNA interference (RNAi) refers to a group of post-transcriptional or transcriptional gene silencing mechanisms conserved from fungi to mammals. It is a phenomenon primarily for the regulation of gene expression, self or nonself depending upon the surrounding factors or conditions. It is done in nature with the help of noncoding RNA molecules to control cellular metabolism and helps in maintaining genomic integrity by preventing the invasion of viruses and mobile genetic elements. It is a simple and rapid method of silencing gene expression in a range of organisms as a consequence of degradation of RNA into short RNAs that activate ribonucleases to target homologous mRNA. The process of RNAi can be mediated by either small interfering RNA (siRNA) or micro RNA (miRNA). The RNAi pathway is triggered by the presence of double-stranded RNA, which is cleaved by the ribonuclease-III domain-containing enzyme Dicer to generate 20–25 nucleotide long siRNA duplexes. siRNA is then loaded onto the RNA-induced silencing complex (RISC), in which an Argonaute (Ago)-family protein, guided by the siRNA, mediates the cleavage of homologous RNAs. Synthetic double-stranded RNA (dsRNA) introduced into cells can selectively and robustly induce suppression of specific genes of interest. Because of its exquisite specificity and efficiency, RNAi is being considered as valuable research tool, not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes.