Specific features of the mature microrna nucleotide sequences can influence the affinity for the human Ago2 and Ago3 proteins

Mature microRNAs (miRNAs) with a length of 20–24 nucleotides are endogenous, small, non-coding RNAs. They program the RNA-induced silencing complex (RISC) to inhibit translation of the mRNAs carrying the sites complementary to these miRNAs. When the RISC contains Ago3, the mRNA translation is inhibited; however, in the case of Ago2, the mRNA can be also cleaved in the center of mRNA/miRNA heteroduplex. Using the earlier developed system ACTIVITY, we have analyzed the published data on the affinity of mature human miRNA sequences for the Ago2 and Ago3 proteins. It has been found that the higher the abundance of YRHB tetranucleotides near the miRNA 3′-end, the higher the miRNA affinity for both proteins (r = 0.613, α < 0.025) and that the miRNA binding to Ago2 increases relative to that Ago3 with the abundance of RHHK tetranucleotides near the miRNA center (r=0.501, α < 0.05). These two patterns allowed us to propose equations for predicting the affinity of mature miRNAs for the Ago2 and Ago3 proteins and to reliably predict the affinity of canonical (α < 0.00025) and noncanonical (α < 0.05) miRNAs for each protein using independent data.