RNA Folding

RNA plays a central role in the life of cells. It is, therefore, important to understand how RNA forms functional native structures endowed with properties such as catalysis, binding of small-molecular-weight ligands, or recognition of proteins. Termed the ''RNA folding problem'' [1], the question is how the primary structure of RNA, a linear polynucleotide, encodes its functional three-dimensional (tertiary) structure.

On the basis of early studies on tRNA and consistent in the first order with more recent studies on ribozymes, a hierarchical model of the folding of RNA has been established [2]. Implicit in this model is the assumption that there are two major structural changes on the way from an ensemble of unfolded RNA molecules to a native state. It is supposed that stable secondary structures, such as hairpins, form rapidly on a microsecond time scale. Subsequent assembly leading to tertiary folding occurs by bringing the secondary structural elements together. This procedure is slower - the time required for tertiary interactions is in the order of milliseconds up to seconds and minutes.

The hierarchical model, the commonly held picture of RNA folding, is not always correct. During recent years outlines of the mechanisms of folding of large RNA molecules are beginning to emerge thanks to several novel experiments in which more advanced techniques, e.g. single molecule-fluorescence spectroscopy [3], synchrotron hydroxyl radical footprinting [4], or temperature gradient gel electrophoresis [5] have been applied. There is growing evidence that the folding kinetics of RNA are complex, involving parallel pathways and kinetic traps that proceed via misfolded structures [6, 7].

In the following discussion, two outstanding discoveries concerning RNA folding are introduced briefly. These findings, which are of importance in the context of our own studies, can be described as:

Coexisting conformers of RNA -one sequence, two ribozymes

UA GC A U CG ggaac G C G G C G C C G G C C C U U C C

0 0

Post a comment