Recognizing micro-RNAs: structural insights into RNA recognition in human micro-RNA biogenesis

Friday 19 October 2012, 12.15PM to 13:15pm

Speaker: Dr Michael Plevin

Micro-RNAs (miRNA) are small non-coding RNAs that regulate gene expression through RNA interference (RNAi). Human miRNAs are generated via a series of enzymatic processing steps. The precursor miRNA (pre-miRNA) is recognized and cleaved by a complex containing the RNase III enzyme Dicer and several non-catalytic accessory proteins. HIV TAR element binding protein (TRBP or TARBP) is a constituent of the Dicer complex, which augments complex stability and potentially functions in substrate recognition and product transfer to the RNA-induced silencing complex (RISC). TRBP is phosphorylated by the MAP kinase Erk and has been proposed to interact with fluoroquinolones, a family of potential anti-cancer drugs. We have analyzed the interaction between the RNA-binding region of TRBP and an oncogenic human miRNA, miR-155, at different points in its biogenesis pathway. Our results show that TRBP cannot differentiate between pre-miR-155, the Dicer substrate, and the miR-155/miR-155* duplex produced by Dicer. These data suggest that TRBP could play a role before and after processing of pre-miRNAs by Dicer. We have also investigated the effect of phosphorylation on TRBP structure and RNA binding, and explored the mode of action of the fluoroquinolone enoxacin.

Location: Biology Lecture Theatre, K018

Admission: All Welcome