Background: RNA-dependent RNA-polymerases of nonsegmented negative-strand RNA viruses (Mononegavirales) harbor multiple catalytic activities. Results: Domain screening and transcomplementation of paramyxovirus polymerase fragments with dimerization tags identifies independent folding-competent domains. Conclusion: Paramyxovirus polymerases harbor at least two independent domains that lack higha...

Intermediates play important roles in RNA folding but can be difficult to characterize when short-lived or not significantly populated. By combining (15)N relaxation dispersion NMR with chemical probing, we visualized a fast (kex=k1+k-1≈423 s(-1)) secondary structural switch directed towards a low-populated (∼3%) partially folded intermediate in tertiary folding of the P5abc subdomain of the 'T...

Evidence is presented suggesting, for the first time, that the protein foldability metric sigma = (T(theta)-T(f))/T(theta), where T(theta) and T(f) are, respectively, the collapse and folding transition temperatures, could be used also to measure the foldability of RNA sequences. These results provide further evidence of similarities between the folding energy landscapes of proteins and RNA. Th...

RNA locally optimal secondary structures provide a concise and exhaustive description of all possible secondary structures of a given RNA sequence, and hence a very good representation of the RNA folding space. In this paper, we present an efficient algorithm that computes all locally optimal secondary structures for any folding model that takes into account the stability of helical regions. Th...

As a consequence of the rugged landscape of RNA molecules their folding is described by the kinetic partitioning mechanism according to which only a small fraction (φF) reaches the folded state while the remaining fraction of molecules is kinetically trapped in misfolded intermediates. The transition from the misfolded states to the native state can far exceed biologically relevant time. Thus, ...

BACKGROUND The ever increasing discovery of non-coding RNAs leads to unprecedented demand for the accurate modeling of RNA folding, including the predictions of two-dimensional (base pair) and three-dimensional all-atom structures and folding stabilities. Accurate modeling of RNA structure and stability has far-reaching impact on our understanding of RNA functions in human health and our abilit...

The term RNA folding is often used synonymously with the prediction of equilibrium structures. Yet many RNAs function thanks to their ability to undergo structural changes. In this contribution we present a systematic overview of existing approaches to the prediction of RNA folding kinetics, and in particular discuss the strengths and limitations of each method.

Transcription is mutagenic, in part because the R-loop formed by the binding of the nascent RNA with its DNA template exposes the nontemplate DNA strand to mutagens and primes unscheduled error-prone DNA synthesis. We hypothesize that strong folding of nascent RNA weakens R-loops and hence decreases mutagenesis. By a yeast forward mutation assay, we show that strengthening RNA folding and reduc...

It has long been appreciated that Mg(2+) is essential for the stabilization of RNA tertiary structure. However, the problem of quantitative prediction for the ion effect in tertiary structure folding remains. By using the virtual bond RNA folding model (Vfold) to generate RNA conformations and the newly improved tightly bound ion model (TBI) to treat ion-RNA interactions, we investigate Mg(2+)-...