On Secondary Structure Rearrangements and Equilibria of Small RNAs

Abstract

Any way up: Secondary structure ambivalence is encountered even in very small RNAs with only 20–40 nucleotides (see scheme). A combined synthetic and NMR spectroscopic approach allows simple and reliable verification of small RNA secondary structure equilibria. This approach is discussed in the context of RNA conformational transitions, biologically relevant RNA switches, RNA secondary structure changes induced by natural nucleoside modifications, and a structure and function ambivalent ribozyme sequence.

Dynamics‐Based Amplification of RNA Function and Its Characterization by Using NMR Spectroscopy

“…[42] This conformational switch, which can be triggered by the chaperone nucleocapsid protein (NcP) and/or divalent ions, may temporally regulate viral replication and packaging functions. [42,43] Self-induced RNA conformational transitions [17] which do not require cellular cofactors are also believed to play a role in RNA-mediated translational [44,45] and transcriptional regulation [46] as well as in the proper folding of ribozymes. [47][48][49][50][51][52][53] Such self-induced transitions are made possible by the fact that secondary motifs such as hairpins can fold at rates faster than RNA synthesis during transcription, thereby resulting in kinetically trapped intermediates.…”

“…Although RNA can fold into more complicated structures than once thought, [14][15][16] these static structures cannot fully account for RNA's functional diversity. Rather, much of RNA's functional diversity appears to derive from dramatic conformational changes that are either self-induced [17] or, more typically, triggered upon binding to cellular cofactors such as proteins, small molecules, divalent ions, and other RNAs. [1,3,18,19] RNA's structural coverage appears to be more limited in scope in the absence of such cofactors and it is often impossible to deduce the fate of an RNA structure following complexation.…”

Review NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings

“…7,8 An emerging theme is that RNA manages to achieve greater functional prowess by having a remarkable ability to undergo large conformational changes in response to specific cellular signals. [9][10][11][12] Cellular signals that can induce changes in RNA conformation include recognition of proteins and small metabolite molecules, metal binding, changes in temperature, and RNA synthesis itself. [9][10][11][12][13] RNA conformational transitions generally serve specific biological functions.…”

“…[9][10][11][12] Cellular signals that can induce changes in RNA conformation include recognition of proteins and small metabolite molecules, metal binding, changes in temperature, and RNA synthesis itself. [9][10][11][12][13] RNA conformational transitions generally serve specific biological functions. For example, stepwise changes in RNA conformation that are induced by successive protein recognition events make it possible to assemble complex ribonucleoproteins (RNPs) in an ordered hierarchical manner.…”

Beyond energy minimization: approaches to the kinetic folding of RNA

“…The renewed interest in RNA as a versatile biomolecule has also inspired diverse experimental approaches to measure folding kinetics in detail, ranging from classical temperature jump experiments [6] to time-resolved NMR spectroscopy [7,8] and single molecular methods [9]. In this contribution we aim to provide an overview of the different computational strategies for modeling RNA folding kinetics and discuss strengths and limitations of the respective approaches.…”