期刊
GENE
卷 345, 期 1, 页码 3-12出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2004.11.043
关键词
RNA secondary structure; non-coding RNA; mRNA stability regulation; AU-rich elements; gene expression; RNA-protein interactions
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, N.-C., Hackermuller, J., Uhl, V., Aszodi, A., Jaritz, M., Auer, M., 2004. mRNA openers and closers: a methodology to modulate AU-rich element controlled mRNA stability by a molecular switch in mRNA conformation. ChemBioChem 5, 1432-1447]. 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. (C) 2004 Elsevier B.V. All rights reserved.
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