title: Mature miRNAs form secondary structure, which suggests their function beyond RISC.
abstract: The generally accepted model of the miRNA-guided RNA down-regulation suggests that mature miRNA targets mRNA in a nucleotide sequence-specific manner. However, we have shown that the nucleotide sequence of miRNA is not the only determinant of miRNA specificity. Using specific nucleases, T1, V1 and S1 as well as NMR, UV/Vis and CD spectroscopies, we found that miR-21, miR-93 and miR-296 can adopt hairpin and/or homoduplex structures. The secondary structure of those miRNAs in solution is a function of RNA concentration and ionic conditions. Additionally, we have shown that a formation of miRNA hairpin is facilitated by cellular environment.Looking for functional consequences of this observation, we have perceived that structure of these miRNAs resemble RNA aptamers, short oligonucleotides forming a stable 3D structures with a high affinity and specificity for their targets. We compared structures of anti-tenascin C (anti-Tn-C) aptamers, which inhibit brain tumor glioblastoma multiforme (GBM, WHO IV) and selected miRNA. A strong overexpression of miR-21, miR-93 as well Tn-C in GBM may imply some connections between them. The structural similarity of these miRNA hairpins and anti-Tn-C aptamers indicates that miRNAs may function also beyond RISC and are even more sophisticated regulators, that it was previously expected. We think that the knowledge of the miRNA structure may give a new insight into miRNA-dependent gene regulation mechanism and be a step forward in the understanding their function and involvement in cancerogenesis. This may improve design process of anti-miRNA therapeutics.
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Belter
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Gudanis
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Rolle
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Piwecka
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Gdaniec
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Mirosława Z
authors.initials: MZ
authors.lastname: Naskręt-Barciszewska
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14, 61-704, Poznan, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Barciszewski
mesh_terms: D001483:Base Sequence; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics; D009690:Nucleic Acid Conformation; D012689:Sequence Homology, Nucleic Acid
chemical_list: D035683:MicroRNAs