Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Structural polymorphism of CAG RNA repeats investigated by single-molecule mechanical unfolding
Structural polymorphism is an intrinsic characteristic of RNA, especially RNA containing repeated sequences. Transcripts including massively expanded trinucleotide repeats are implicated in many human diseases due to their cellular toxicity. Here we used optical tweezers to unfold RNAs with CAG repeats one molecule at a time. Unfolding trajectories of the RNAs indicated rapid transitions between numerous intermediates with distinctive end-to-end distances, suggesting a flat but rugged folding energy landscape with many shallow local minima. Individual RNAs were nanomanipulated into intermediate structures and their conformational dynamics among local energy minima was monitored in real time. This experimental approach will enable study of other simple sequence repeats, which account for 3% of the human genome.
1College of Nanoscale Science and Engineering SUNY Polytechnic Institute