RNAi: An Effective Tool for Elucidating Gene Functions and a New Class of Drugs

RNAi is a mechanism in living cells that helps determine which genes are active and how active they are. It is a naturally occurring pathway for the regulation of gene expression in which small RNA molecules lead to the destruction of messenger RNA (mRNA) with complementary nucleotide sequences. RNAi has an important role in defending cells against parasitic genes – viruses and transposons – but also in directing development and gene expression in general.

Two types of small RNA molecules are central in the RNAi pathway (Figure 1.1). One is small interfering RNA (siRNA), sometimes known as short-interfering RNA or silencing RNA, a class of 20 to 25 nucleotide-long double-stranded RNA (dsRNA) molecules, and the other is microRNA (miRNA), a class of endogenous dsRNA molecules of about 21 to 23 nucleotides in length. Both siRNA and miRNA can bind to other specific RNAs and either increase or decrease their activity, usually by preventing an mRNA from producing a protein.

siRNA. The RNAi pathway is controlled by endoribonuclease-containing complexes known as RNA-induced silencing complexes (RISCs) and initiated by an enzyme called Dicer in the cell's cytoplasm (Figure 1.1). In the initiation step, the Dicer cleaves long dsRNA molecules into siRNAs. An siRNA assembles into a RISC and unwinds into two single strands.