RNA interference, or RNAi, is a well-recognized and evolutionarily conserved pathway of cellular defense that has been observed in nearly every eukaryotic organism studied.
The functional component that directs RNAi is a 21-23 nucleotide (nt) RNA duplex, also know as a small interfering RNA or siRNA. In nature these duplexes are produced by the cell in response to a number of events that generate long double-stranded RNA transcripts. Examples of such events include viral replication, sequence transposition and abnormal transcription of native genes.
This pathway is particularly strong in invertebrates, which do not have the interferon system; in fact, it is thought to be their primary defense mechanism against viral infection.
Importantly, synthetic siRNAs can also be introduced into cells by a number of mechanisms, intervening in this naturally occurring pathway, as shown in the schematic below.
Move your cursor over a letter to view the description of the corresponding step in the mechanism.
Mechanism of RNA interference
Why is this pathway so significant to biomedical research?
The completion of the Human Genome Project has unleashed a flood of sequence information that now allows investigators to study all of the approximately 21,000 human genes. The precise function of many genes is understood, but that of many more genes is not.
By exploiting this naturally-occurring pathway to silence a gene, it becomes possible to understand exactly what that gene does. Researchers can also study metabolic pathways in their entirety to identify how the genes function together to regulate the activity of the pathway.
The ultimate goal of this research is to understand the function of all human genes. The knowledge gained will accelerate the development of a new generation of therapeutics to treat disease.