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

• Published in: Scientific reports Vol. 10; no. 1; p. 453
• Main Authors: Gangemi, C. M. A., Alaimo, S., Pulvirenti, A., García-Viñuales, Sara, Milardi, D., Falanga, A. P., Fragalà, M. E., Oliviero, G., Piccialli, G., Borbone, N., Ferro, A., D’Urso, A., Croce, C. M., Purrello, R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-01-2020; Nature Publishing Group
• Subjects: 140/131; 45/29; 631/45/500; 639/638/45/500; Base Sequence; Biological activity; Computer applications; Epidermal growth factor receptors; ErbB Receptors - deficiency; ErbB Receptors - genetics; Gene expression; Gene Silencing; Humanities and Social Sciences; MicroRNAs - chemistry; MicroRNAs - genetics; miRNA; multidisciplinary; Non-coding RNA; Nucleic Acid Conformation; Protein structure; Proto-Oncogene Proteins c-met - deficiency; Proto-Oncogene Proteins c-met - genetics; Science; Science (multidisciplinary); Secondary structure; Sequence Analysis, RNA
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-57289-8

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