Large RNAs can collapse into compact conformations well before the stable formation of the tertiary contacts that define their final folds. This study identifies likely physical mechanisms driving these early compaction events in RNA folding. We have employed time-resolved small-angle X-ray scattering to monitor the fastest global shape changes of the Tetrahymena ribozyme under different ionic ...

RNA sequences fold into their native conformations by means of an adaptive search of their folding energy landscapes. The energy landscape may contain one or more suboptimal attractor conformations, making it possible for an RNA sequence to become trapped in a suboptimal attractor during the folding process. How the probability that an RNA sequence will find a given attractor before it finds an...

The folding of ribosomal RNAs is central to the biogenesis mitoribosome and a complex, stepwise process. Five recent cryo-EM studies detail late steps maturation human mitoribosomal large subunit RNA that forms catalytic core ribosome: peptidyl transferase center (PTC).

The RNA folding trajectory features numerous off-pathway folding traps, which represent conformations that are often equally as stable as the native functional ones. Therefore, the conversion between these off-pathway structures and the native correctly folded ones is the critical step in RNA folding. This process, referred to as RNA refolding, is slow, and is represented by a transition state ...

Mg2+ ions are very effective at stabilizing tertiary structures in RNAs. In most cases, folding of an RNA is so strongly coupled to its interactions with Mg2+ that it is difficult to separate free energies of Mg2+-RNA interactions from the intrinsic free energy of RNA folding. To devise quantitative models accounting for this phenomenon of Mg2+-induced RNA folding, it is necessary to independen...

RNA folding is an essential aspect underlying RNA-mediated cellular processes. Many RNAs, including large, multi-domain ribozymes, are capable of folding to the native, functional state without assistance of a protein cofactor in vitro. In the cell, trans-acting factors, such as proteins, are however known to modulate the structure and thus the fate of an RNA. DEAD-box proteins, including Mss11...

We introduce here a heuristic approach to kinetic RNA folding that constructs secondary structures by stepwise combination of building blocks. These blocks correspond to subsequences and their thermodynamically optimal structures. These are determined by the standard dynamic programming approach to RNA folding. Folding trajectories are modeled at base-pair resolution using the Morgan-Higgs heur...

We report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to dete...

Structured RNA molecules play roles in central biological processes and understanding the basic forces and features that govern RNA folding kinetics and thermodynamics can help elucidate principles that underlie biological function. Here we investigate one such feature, the specific interaction of monovalent cations with a structured RNA, the P4-P6 domain of the Tetrahymena ribozyme. We employ ...