Nadeska Montalvan
Mentors: Martina Zafferani1, Amanda E. Hargrove1,2
1Department of Chemistry
2Department of Biochemistry
Out of the total RNA transcribed in cells, only 1.5% is translated into proteins. About 70% of the rest of the human genome is transcribed into non-coding RNA (ncRNA). While the roles of most ncRNAs remain unknown, several ncRNAs have been found to be overexpressed in various cancers which makes them attractive therapeutic targets. Small molecules have been successfully developed to bind to RNAs. However, it remains unclear whether small molecules selectively bind to different RNA sequences with similar structural motifs. Thus, we aimed to screen a large in-house small molecule library against three RNA sequences with triple helix structures, namely MALAT1, NEAT1 and PAN. We hypothesized that most molecules that would bind to one RNA would bind to the other two, indicating low selectivity. We used high-throughput screening to determine which small molecules bound to each RNA. Surprisingly, the screening revealed several small molecules that selectively bind to each of the three triple helices. Additionally, findings yielded a 100-fold higher hit rate than the average rates of high-throughput screenings against general RNA targets. Current efforts are focused on evaluating the newly identified selective small molecules against their respective RNA target to determine any possible unique properties of selective binders.
