Endogenous and artificial miRNAs explore a rich variety of conformations: a potential relationship between secondary structure and biological functionality

Mature microRNAs are short non-coding RNA sequences which upon incorporation into the RISCribonucleoprotein complex, play a crucial role in regulation of gene expression. However, miRNAs canexist within the cell also as free molecules fulfilling their biological activity. Therefore, it is emergingthat in addition to sequence even the structure adopted by mature miRNAs might play an importantrole to reach the target. Indeed, we analysed by several spectroscopic techniques the secondarystructures of two artificial miRNAs selected by computational tool (miR-Synth) as best candidates tosilence c-MET and EGFR genes and of two endogenous miRNAs (miR-15a and miR-15b) having thesame seed region, but different biological activity. Our results demonstrate that both endogenous andartificial miRNAs can arrange in several 3D-structures which affect their activity and selectivity towardthe targets.