Inst. f. Informatik   
Uni Leipzig

Bioinformatics Preprint 04-016

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The Effect of RNA Secondary Structures on RNA-Ligand Binding and the Modifier RNA Mechanism: A Quantitative Model

Jörg Hackermüller, Nicole-Claudia Meisner, Manfred Auer, Markus Jaritz, Peter F. Stadler

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RNA-ligand binding often depends crucially on the local RNA secondary structure at the binding site. We develop here a model that quantitatively predicts the effect of RNA secondary structure on effective RNA-ligand binding activities based on equilibrium thermodynamics and the explicit computations of partition functions for the RNA structures. A statistical test for the impact of a particular structural feature on the binding affinities follows directly from this approach. The formalism is extended to describing the effects of hybridizing small ``modifier RNAs'' to a target RNA molecule outside its ligand binding site. We illustrate the applicability of our approach by quantitatively describing the interaction of the mRNA stabilizing protein HuR with AU-rich elements [Meisner et al. (2004), Chem. Biochem. in press]. We discuss our model and recent experimental findings demonstrating the effectivity of modifier RNAs in vitro in the context of the current research activities in the field of non-coding RNAs. We speculate that modifier RNAs might also exist in nature; if so, they present an additional regulatory layer for fine-tuning gene expression that could evolve rapidly, leaving no obvious traces in the genomic DNA sequences.

RNA secondary structure, non-coding RNA, mRNA stability regulation, AU-rich elements, gene expression.

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