Thursday,
November 20, 2008, Condensed Matter Biological Physics Seminar, Maumita
Mandal, Chemistry Department, Carnegie Mellon Univ., "Mechanical forces to
probe RNA structural dynamics in
single-molecules using optical-tweezers", 4:30 PM, Doherty Hall A310, CMU
Abstract:
The physical properties of RNA-based molecular machines are relatively less studied in biological sciences. RNA unfolding and folding reactions in physiological conditions can be facilitated by mechanical force one molecule at a time. We have developed single-molecule optical-tweezer techniques to study how mechanical forces affect the conformational dynamics and chemistry of RNA molecules. A single-molecule of RNA is held between two microspheres - one trapped by the lasers and the other held by a micropipette. When a tethered molecule is extended and relaxed, the force properties are unique mechanical fingerprints that directly indicate the folding transitions of individual structural domains. Using a modified force-jump and constant-force measurements, we observed both the slow and the fast kinetics of conformational rearrangements within a base-pair resolution. RNAs play an important role in gene regulation and enzymatic activities, earlier known to be the realm of proteins alone. Understanding the structural rearrangements in RNAs under different cellular conditions is important as misfolding events often leads to diseased state. I will discuss on how dynamic readouts of the RNA structural rearrangements help transcriptional machinery to make genetic decisions, as evident from single molecule experiments.