Investigation of structural switch that regulates pre-miR-92a processing by NMR

MicroRNAs (miRNAs) regulate gene expression in a variety of biological pathways such as development and tumorigenesis. miRNAs are initially expressed as a long primary transcripts (pri-miRNA) which are processed to yield pre-miRNAs and ultimately mature miRNAs. The miR-17-92a cluster, also known as ‘oncomiR-1’ is a polycistronic pri-miRNA that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. OncomiR-1 includes six constitute miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. However, the structural mechanism that regulate the differential processing still remain unclear.
NMR is a key technique that has significantly advanced our understanding of RNA structure and dynamics. In vitro processing assays indicate that pre-miR-92a processing is inhibited relative to other miRs within oncomiR-1. We are interested in uncovering the structural basis for the differential processing by NMR. NPSL2 has been identified as an inhibitor of pre-miR-92a processing. Therefore, in this work we determined the solution structure of NPSL2. Our data suggest that NPSL2 is dynamic, and we hypothesize that the dynamics are linked to regulation of processing. Our ongoing efforts will investigate the mechanism of the structural switch that promotes premiR-92a processing in the context of the full-length oncomiR-1 RNA.