Long-Range Distance Measurements on Nucleic Acids in Cells by Pulsed EPR Spectroscopy

Short complementary B-form DNA oligomers, 6 to 20 base pairs in length, are found to exhibit nematic and columnar liquid crystal phases, even though such duplexes lack the shape anisotropy required for liquid crystal ordering. Structural study shows that these phases are produced by the end-to-end adhesion and consequent stacking of the duplex oligomers into polydisperse anisotropic rod-shaped aggregates, which can order into liquid crystals. Upon cooling mixed solutions of short DNA oligomers, in which only a small fraction of the DNA present is complementary, the duplex-forming oligomers phase-separate into liquid crystal droplets, leaving the unpaired single strands in isotropic solution. In a chemical environment where oligomer ligation is possible, such ordering and condensation would provide an autocatalytic link whereby complementarity promotes the extended polymerization of complementary oligomers.

A wealth of information on RNA folding and ribonucleoprotein assembly has emerged from analyses of structures and from the use of innovative biophysical tools. Although integrating data obtained from static structures with dynamic measurements presents major challenges, such efforts are opening new vistas on the RNA folding landscape.