A Potassium Ion-Dependent RNA Structural Switch Regulates Human Pre-miRNA 92b Maturation

作者：Arachchilage Gayan Mirihana; Dassanayake Arosha C; Basu Soumitra^*

来源：Chemistry & Biology, 2015, 22(2): 262-272.

DOI：10.1016/j.chembiol.2014.12.013

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 premiRNA 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.

• 出版日期2015-2-19