Long noncoding RNAs (lncRNAs) do not code for proteins but function as RNAs. Because the functions of an RNA rely on either its sequence or secondary structure, lncRNAs should be folded at least as strongly as messenger RNAs (mRNAs), which serve as messengers for translation and are generally thought to lack secondary structure-dependent RNA-level functions. Contrary to this prediction, analysi...

The folding of linear polymers into discrete three-dimensional structures is often required for biological function. The formation of long-lived intermediates is a hallmark of the folding of large RNA molecules due to the ruggedness of their energy landscapes. The precise thermodynamic nature of the barriers (whether enthalpic or entropic) that leads to intermediate formation is still poorly ch...

The folding and catalytic function of RNA molecules depend on their interactions with divalent metal ions, such as magnesium. As with every molecular process, the most basic knowledge required for understanding the close relationship of an RNA with its metal ions is the stoichiometry of the interaction. Unfortunately, inventories of the numbers of divalent ions associated with unfolded and fold...

Mg(2+) is essential for the proper folding and function of RNA, though the effect of Mg(2+) concentration on the free energy, enthalpy, and entropy landscapes of RNA folding is unknown. This work exploits temperature-controlled single-molecule FRET methods to address the thermodynamics of RNA folding pathways by probing the intramolecular docking/undocking kinetics of the ubiquitous GAAA tetral...

The aim of the inverse folding problem for RNA is, given a target structure like e.g. the one depicted in Fig. 1, find a sequence that folds into this structure. In this project we will exclusively focus on the secondary structure. The main driving force behind RNA structure formation is the creation of base pairs similar to the ones observed in the DNA double helical structure. In RNA thymine ...

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovere...

SUMMARY Chemical mapping experiments allow for nucleotide resolution assessment of RNA structure. We demonstrate that different strategies of integrating probing data with thermodynamics-based RNA secondary structure prediction algorithms can be implemented by means of soft constraints. This amounts to incorporating suitable pseudo-energies into the standard energy model for RNA secondary struc...

Based on the complete ensemble of hairpin conformations, a statistical mechanical model that combines the eigenvalue solutions of the rate matrix and the free-energy landscapes has been able to predict the temperature-dependent folding rate, kinetic intermediates, and folding pathways for hairpin-forming RNA sequences. At temperatures higher than a "glass transition" temperature, T(g), the eige...

RNA folding landscapes have been described alternately as simple and as complex. The limited diversity of RNA residues and the ability of RNA to form stable secondary structures prior to adoption of a tertiary structurewould appear to simplify folding relative to proteins. Nevertheless, there is considerable evidence for long-lived misfolded RNA states, and these observations have suggested rug...

BACKGROUND Metal ions play a critical role in the stabilization of RNA structures. Therefore, accurate prediction of the ion effects in RNA folding can have a far-reaching impact on our understanding of RNA structure and function. Multivalent ions, especially Mg²⁺, are essential for RNA tertiary structure formation. These ions can possibly become strongly correlated in the close vicinity of RNA...