Statistical Potentials for Hairpin and Internal Loops Improve the Accuracy of the Predicted RNA Structure

Abstract

RNA is directly associated with a growing number of functions within the cell. The accurate prediction of different RNAs higher-order structure from their nucleic acid sequences will provide insight into their functions and molecular mechanics. We have been determining statistical potentials for a collection of structural elements that is larger than the number of structural elements determined with experimentally determined energy values. The experimentally derived free-energies and the statistical potentials for canonical base pair stacks are analogous, demonstrating that statistical potentials derived from comparative data can be used as an alternative energetic parameter. A new computational infrastructure - RNA Comparative Analysis Database (rCAD) - that utilizes a relational database was developed to manipulate and analyze very large sequence alignments and secondary structure datasets. Using rCAD, a richer set of energetic parameters for RNA fundamental structural elements including hairpin and internal loops was determined. A new version of RNAfold was developed to utilize these statistical potentials. Overall, these new statistical potentials for hairpin and internal loops integrated into the new version of RNAfold demonstrated significant improvements in the prediction accuracy of RNA secondary structure.

Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS

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