What Is RNA Interference
The human genome is made up of thousands of genes, each having a specific biological role and influencing the body’s function through a process known as expression. Gene expression consists of the production of ribonucleic acids (RNAs) which either translate genetic information encoded by a gene into gene-specific protein products (protein-coding RNAs), or function on their own (protein non-coding RNAs). The process of gene expression is tightly regulated. Some diseases are caused by the abnormal behavior of certain genes. A natural biological pathway, known as RNA interference (or RNAi), functions in virtually every cell in the body to regulate gene expression and to ensure that biological processes take place in concert. RNAi also has an important role in defending cells against parasitic nucleotide sequences, such as viruses and transposons. More specifically, RNAi is a biological process in which specific targeted (complementary) RNA molecules inhibit the expression of specific genes by preventing their encoded RNAs from being translated into proteins (Figure 1). The discovery of RNAi in the late 1990s was a breakthrough in understanding the genome and cell function. The importance of this discovery was recognized by awarding the Nobel Prize for Physiology or Medicine to Craig Mello and Andrew Fire in 2006.
The effectors of RNAi belong to several RNA classes expressed in the genome, whereas two types of short double-stranded RNA (dsRNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – play the central role in RNAi. The RNAi pathway is initiated by the enzymes Drosha and Dicer which cleave longer dsRNA molecules into short ~21-23 nucleotide dsRNA fragments comprised of the passenger strand and the guide strand. Such dsRNAs are recognized by a specific protein complex – so-called RNA-Induced Silencing Complex (RISC). The passenger strand is degraded, and the guide strand, that is complementary to an RNA target sequence, is incorporated into it. Such loaded RISC mediates post-transcriptional gene silencing, which occurs when the guide strand pairs with a complementary sequence in a targeted RNA molecule and induces its cleavage by Argonaute 2 (Ago2), the catalytic component of the RISC (or degradation via other RNA decay pathways) resulting in deactivation, or silencing, of the desired gene.