Using this reconstitution hypothesis, we propose to predict, in a “bottom-up” manner, the folding behavior of natural RNAs and RNA-protein complexes. The results will significantly advance our understanding, either providing strong evidence for the reconstitution hypothesis and demonstrating predictive power via multiple non-trivial tests, or identifying complexities in RNA and RNA/protein behavior that can be tested and incorporated into next-generation models.
Thermodynamic stabilities are not the sole determinant of the conformational distributions of cellular RNAs especially during transcription. This project focuses on conformational search and capture probability model of ‘simple’ tertiary RNA folding, the impacts of transcription using the same RNA and still simpler, more pliable model RNAs that can be used to systematically dissect features and factors important in co-transcriptional folding.
This project is dedicated to achieving this level of understanding for a ubiquitous building block element of RNA tertiary structure: the helix-junction-helix (HJH) motif. Our studies are made possible by recent breakthroughs in experimental techniques for dissecting RNA structure ensembles. This study will mark the beginning of an effort aimed at comprehensively characterizing the entire HJH ‘periodic table’.
This project focuses the ubiquitous ion atmosphere, which profoundly influences the overall folding of all complex RNAs. We have chosen to work with simple, structurally well-defined constructs to isolate electrostatic interactions involving the ion atmosphere to their basic core elements. This basic, comprehensive, and rich data is used to rigorously develop and test state-of-the-art electrostatic models and theories that can be applied for prediction and used as tools for design in more complicated RNA systems.
