The levels of mature microRNAs (miRNA), short non-coding RNAs that regulate the translation of more than ~50% of human genes, are dysregulated in many cancers and neurodegenerative diseases. The miRNAs pathway involves the nuclear processing of primary-miRNA by Drosha into ~90-110 nucleotide-long precursor-miRNA (pre-miRNAs) that undergo further processing in the cytosol by Dicer cleavage to produce mature miRNAs that are ultimately incorporated into the RNA induced silencing complex. Recently, G-quadruplex (G4) secondary structure has been implicated in regulating this maturation pathway by downregulating Dicer cleavage of pre-miRNA. In this study, we hypothesized that pre-miR-125b-2, a guanine rich transcript, forms a G-quadruplex structure which downregulates its Dicer processing. To characterize this G4 structure, we used biophysical methods including <sup>1</sup>H NMR, CD, and UV-Vis spectroscopy, as well as native PAGE. Moreover, we analyzed the interactions of pre-miR-125b-2 G4 structure with G4-selective RNA binding proteins and its Dicer processing using fluorescence spectroscopy.

Regulation of miRNA maturation pathway by pre-miRNA G-quadruplex structure

255th National Meeting (2018)

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