Figure 1. Exogenous RNAi by shRNAs may compete with the microRNA pathway.
A) Schematic of the biogenesis pathway for miRNAs which requires Drosha and Dicer to sequentially and specifically cut the miRNA and shRNA precursor into a small RNA duplex. The Guide strand will be incorporated into the Argonaute (Ago1– 4) proteins and the Ago2-RISC targets mRNA degradation. shRNAs may compete with miRNAs for specific limiting factors like Ago2 and Exportin5. B) The secondary structure for the priand pre-miRNA-30 from mouse, top, and Xenopus, bottom, with the miR-30-5p noted in red and the miR-30-3p noted in blue. There is conservation in the mechanism that directs greater accumulation of miR-30-5p as the Guide strand (red) in both mouse (10 fold to 300 fold, (55)) and frog (3 fold, (56)).