Place: MSL Auditorium

RNA Folding and the Cellular Environment: How Solvent Modulates RNA Stability

Many RNAs switch between folded, partially unfolded, or other alternative conformations in carrying out their functions in vivo. These RNA conformational equilibria must have been 'tuned' by natural selection to operate in the context of the cellular milieu of inorganic ions (K+ and Mg2+), organic ions (polyamines), and frequently high concentrations of the small,neutral organic compounds (osmolytes) that regulate cell turgor pressure. To understand how RNAs function in vivo, it will ultimately be necessary to map the thermodynamic network of interactions taking place between all of these cellular components.

In this talk I will outline our work on two components that strongly stabilizemany RNA structures, but by contrasting strategies. Mg2+ stabilizes compact, native RNA conformations relative to more extended partially unfolded states, largely because Mg2+ can take advantage of a highly negative RNA electrostatic potential at lower entropic cost than monovalent ions. The osmolyte TMAO has a strongly unfavorable interaction with the RNA backbone, and therefore stabilizes compact conformations in which the backbone is inaccessible to solvent. The extent of backbone dehydration, which can be quantified in these experiments, is surprisingly large.

Extrapolation of these in vitro findings to RNAfolding in vivo is complicated by our observation that the effects of ions and osmolytes may be far from additive; TMAO and Mg2+ are in fact strongly antagonistic. Using several different methods to measure solute and RNA activities in multi-component solutions, we are defining the kinds of "crosstalk" between solvent components that may be important for RNA function in vivo.