A Model for Human RISC Function Involving miRNA and siRNA

<p>RISC contains Ago2 (red), Ago1 (green), RCK/p54 (blue, labeled p54), and other known (e.g., Dicer and TRBP) and unidentified proteins (pink) and is distributed throughout the cytoplasm. siRISC binds to its target mRNA by perfectly matching base pairs, cleaves the target mRNA for degradation, recycles the complex, and does not require P-body structures for its function. Multiple numbers <i>(n)</i> of miRISC bind to target mRNA by forming a bulge sequence in the middle that is not suitable for RNA cleavage, accumulate in P-bodies, and repress translation by exploiting global translational suppressors such as RCK/p54. The translationally repressed mRNA is either stored in P-bodies or enters the mRNA decay pathway for destruction. Depending upon cellular conditions and stimuli, stored mRNA can either re-enter the translation or mRNA decay pathways.