[The nucleotide sequence features of the mature microRNA seem to be responsible for the affinity to human Ago2 AND Ago3 proteins].

Mature miRNA of 20-24 nt in length are the endogenous sncRNA. They programs RISC to regulate functioning of mRNA with complimentary sites for these miRNAs. In case of Ago3 protein present in human RISC miRNAs direct inhibition of translation, whereas in case of Ago2 is in RISC, than mRNA cleavage in the middle of miRNA/mRNA heteroduplex is also possible. Using ACTIVITY system, that we developed earlier, we analyzed published data on miRNA affinity to human Ago2 and Ago3 proteins. We found increase in miRNA affinity to both Ago2 and Ago3 with the increase of the YRHB tetranucleotide abundance near 3'-end of these miRNAs (r = 0.613, alpha < 0.025). We also found that miRNA tendency to bind Ago2 in favor of Ago3 increases with the RHHK tetranucleotide abundance near miRNA center (r = 0.501, alpha < 0.05). Using these two findings we proposed two formulas to predict miRNA affinity to Ago2 and Ago3 proteins based on the YRHB and RHHK abundances within this arbitrary miRNA. Thereby we made reliable predictions of miRNA affinity to these proteins in RISC for both canonical (alpha < 0.00025) and non-canonical (alpha < 0.05) miRNAs in comparison with independent experimental data.