RNA dynamics: it is about time

Abstract

Many recently discovered RNA functions rely on highly complex multistep conformational transitions that occur in response to an array of cellular signals. These dynamics accompany and guide, for example, RNA cotranscriptional folding, ligand sensing and signaling, site-specific catalysis in ribozymes, and the hierarchically ordered assembly of ribonucleoproteins. RNA dynamics are encoded by both the inherent properties of RNA structure, spanning many motional modes with a large range of amplitudes and timescales, and external trigger factors, ranging from proteins, nucleic acids, metal ions, metabolites, and vitamins to temperature and even directional RNA biosynthesis itself. Here, we review recent advances in our understanding of RNA dynamics as highlighted by biophysical tools.

Figure 1

Role of RNA conformational transitions in (a) co-transcriptional folding (b) sensing and signaling transactions by riboswitches (c) catalysis (star, reaction chemistry; orange double arrow, global motions; green double arrow, local motions) and (d) hierarchical ribonucleoprotein assembly.

Figure 2

Time-chart of dynamic processes in RNA and corresponding biophysical techniques that can be applied towards their characterization.

Figure 3

Proposed multi-step mechanisms for the ligand-induced conformational transition in the aptamer domains of riboswitches. Shown are mechanisms based on fluorescence studies for (a) the C74U variant of the B. subtilis xpt-pbuX guanine riboswtich [13], (b) the Vibrio vulnificus adenosine deaminase riboswitch, and (c) the Escherichia coli thiamine pyrophosphate riboswitch [15], as well as NMR studies for (d) the B. subtilis xpt-pbuX guanine riboswitch [16••] and (e) the stem-loop IV thermosensor element from the repressor of heat-shock gene expression (ROSE).

Figure 4

Spatially structured inter-helical motional trajectory in free HIV-1 TAR RNA visualized using NMR techniques [47••].