MicroRNAs are endogenous small non-coding RNAs about 21 nucleotides in length that inhibit the expression of target genes primarily at the post-transcriptional level. The target recognition of microARN is sequence-specific and requires a partial complementarity between the microRNA and target sequences that are present on the mRNA molecules. microRNAs are part of an effector complex, miRISC, containing multiple proteins which can participate to a repression of translation and/or promotes destabilization of the target mRNA. The mechanism of microRNA silencing is not completely understood to date, but it is assumed that it is globally less potent than that of siRNA acting on perfect targets. By using fluorescent proteins expressing reporter plasmids and flow cytometry, we observed an efficient silencing by microRNA which does not require more active complexes than the perfect target silencing and cannot be easily saturated. This suggests that in cells in culture, microRNA silencing works in a catalytic manner leading to mRNA degradation. In addition, our data also indicates that the efficiency of microRNA silencing is variable among cells and can be almost completely abrogated under some conditions contrary to the siRNA silencing which is active in all cells. As we observed that the protein Ago2 is the only member of Ago family that is implicated in the microRNA silencing, it follows that the regulation of microRNA silencing acts after the formation of the core complex (Ago2/small RNA). So the difference between the silencing in the perfect and imperfect mode are not what is usually proposed, but pertain to a level of cellular control, which remains to be deciphered.
