Human Argonaute-2: For All Your RNA Slicing Needs

Human cells have the remarkable capability to regulate protein production by degrading target mRNA by two pathways: RNA interference (RNAi) and micro RNA (miRNA). Central to these pathways is the protein Argonaute-2 (Ago-2). In the RNAi pathway, small RNAs derived from viruses are used by Ago-2 to slice virus mRNA, protecting the cells from infection. In the miRNA pathway, Ago-2 utilizes naturally occurring miRNA to slice cellular mRNAs to control protein production. Ago-2 works by binding small (~22 nucleotide) regulatory RNAs (siRNA and miRNA) to target mRNA by base pairing. Ago-2 attaches to the phosphate backbone of the regulatory RNA, that guides Ago-2 to the target RNA. The RNase domain of Ago-2 (containing His807, Asp669, Asp597, and Glu637 in its active site) then “slices” the target to initiate degradation. Scientists can reduce the level of disease-causing proteins (for example, in breast cancer) using the siRNA pathway. Determining the structure of Ago-2 allowed researchers to understand how th...