title: A potassium ion-dependent RNA structural switch regulates human pre-miRNA 92b maturation.
abstract: MicroRNAs (miRNAs) are an important set of oligonucleotide sequences with a biogenesis that involves Dicer-mediated cleavage as a critical step. Dicer cleaves the precursor miRNA (pre-miRNA) stem-loop structure to produce the mature miRNA. Using bioinformatics analysis, we discovered the presence of putative G-quadruplex (GQ)-forming sequences in about 16% of pre-miRNAs. We report the existence of a GQ as an alternative to the canonical stem-loop structure in the clinically important human pre-miRNA 92b. GQ formation led to unwinding of the stem-loop structure imparting resistance to Dicer-mediated cleavage both in vitro and in vivo. A potential K(+) ion-dependent equilibrium between GQ and the stem-loop structure has the ability to regulate the Dicer-mediated maturation of pre-miRNA 92b, which consequently affects target gene silencing. These findings unravel a new mechanism of regulation in pre-miRNA maturation, albeit at the RNA structure level.
authors: Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA.
authors: Gayan
authors: G
authors: Mirihana Arachchilage
authors: Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA.
authors: Arosha C
authors: AC
authors: Dassanayake
authors: Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA. Electronic address: sbasu@kent.edu.
authors: Soumitra
authors: S
authors: Basu
mesh_terms: D020413:3' Untranslated Regions; D002942:Circular Dichroism; D054856:G-Quadruplexes; D057809:HEK293 Cells; D006801:Humans; D007477:Ions / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry*; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044366:Transition Temperature
chemical_list: D020413:3' Untranslated Regions; D007477:Ions; D035683:MicroRNAs; D012322:RNA Precursors; D011188:Potassium