RNA is a molecular machine that carries out a large number of tasks within the cell. The awareness of its central involvement in biological processes is among the most remarkable scientific discoveries of the last thirty years. In the earliest models, RNA's role was relegated to that of messenger, passively copying and transporting pieces of the genetic code. Recent research illustrates its active participation in executing the instructions present in the genome. RNA's widely-varying functions range from 'splicing'genes together to regulating the concentrations of key metabolites. Many of these newly discovered roles rely on RNA folding to specific functional structures and responding to the environment by dynamically changing shape. The goal of this proposal is to obtain an atomically detailed picture of the RNA folding process. This vision is beyond current experimental capabilities, but is on the horizon for new simulation methods. However, simulation must be validated by observation. This project identifies important landmarks along the folding pathway of a small RNA that can be detected with advanced experimental tools. Observation of the time scale for and sequences of events will be determined by experiment, and used to validate simulations, which provide insight into atomically detailed processes. The expanding appreciation of RNA's biological roles brings recognition of its potential as a new target for drugs. Insights gained int the atomic level workings of RNA folding and dynamics may assist with RNA based drug design.

Public Health Relevance

The need for new antibiotics cannot be overstated as bacteria continue to acquire antibiotic resistance. Efforts are intensifying to develop drugs that specifically target bacterial RNAs. However, a lack of detailed understanding regarding small molecule binding by RNA limits drug development and will be facilitated by insights gained here into atomically detailed motions of RNA.

National Institute of Health (NIH)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Preusch, Peter
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Cornell University
Engineering (All Types)
Biomed Engr/Col Engr/Engr Sta
United States
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Tokuda, Joshua M; Pabit, Suzette A; Pollack, Lois (2016) Protein-DNA and ion-DNA interactions revealed through contrast variation SAXS. Biophys Rev 8:139-149
Nguyen, Hung T; Pabit, Suzette A; Pollack, Lois et al. (2016) Extracting water and ion distributions from solution x-ray scattering experiments. J Chem Phys 144:214105
Chen, Yujie; Pollack, Lois (2016) SAXS studies of RNA: structures, dynamics, and interactions with partners. Wiley Interdiscip Rev RNA 7:512-26
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Sutton, Julie L; Pollack, Lois (2015) Tuning RNA Flexibility with Helix Length and Junction Sequence. Biophys J 109:2644-53
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Meisburger, Steve P; Warkentin, Matthew; Chen, Huimin et al. (2013) Breaking the radiation damage limit with Cryo-SAXS. Biophys J 104:227-36
Pabit, Suzette A; Sutton, Julie L; Chen, Huimin et al. (2013) Role of ion valence in the submillisecond collapse and folding of a small RNA domain. Biochemistry 52:1539-46
Meisburger, Steve P; Sutton, Julie L; Chen, Huimin et al. (2013) Polyelectrolyte properties of single stranded DNA measured using SAXS and single-molecule FRET: Beyond the wormlike chain model. Biopolymers 99:1032-45

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