Following RNA folding from local and global perspectives

A significant driving force to RNA folding is the localized neutralization of the highly electronegative charge of the phosphodiester backbone by cations. Thus, the folding of RNA molecules into biologically active three-dimensional structures is marked by global compaction resulting from this charge neutralization and the formation of the numerous local noncovalent interactions that stabilize discrete structures. Understanding the relative contribution to folding of sequence nonspecific charge neutralization and formation and breaking of sequence specific noncovalent interactions are critical to understanding molecular mechanisms of RNA folding. This article explores the concomitant use of techniques that track global and local changes in RNA conformation in order to partition nonspecific and specific contributions to the folding process.