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Nucleic Acids Res. 2012 Jan;40(2):892-904. doi: 10.1093/nar/gkr751. Epub 2011 Sep 21.

New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation.

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1
Departments of Chemistry & Biophysics, The University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109-1055, USA.

Abstract

Recent studies have shown that topological constraints encoded at the RNA secondary structure level involving basic steric and stereochemical forces can significantly restrict the orientations sampled by helices across two-way RNA junctions. Here, we formulate these topological constraints in greater quantitative detail and use this topological framework to rationalize long-standing but poorly understood observations regarding the basic behavior of RNA two-way junctions. Notably, we show that the asymmetric nature of the A-form helix and the finite length of a bulge provide a physical basis for the experimentally observed directionality and bulge-length amplitude dependence of bulge induced inter-helical bends. We also find that the topologically allowed space can be modulated by variations in sequence, particularly with the addition of non-canonical GU base pairs at the junction, and, surprisingly, by the length of the 5' and 3' helices. A survey of two-way RNA junctions in the protein data bank confirms that junction residues have a strong preference to adopt looped-in, non-canonically base-paired conformations, providing a route for extending our bulge-directed framework to internal loop motifs and implying a simplified link between secondary and tertiary structure. Finally, our results uncover a new simple mechanism for coupling junction-induced topological constraints with tertiary interactions.

PMID:
21937512
PMCID:
PMC3258142
DOI:
10.1093/nar/gkr751
[Indexed for MEDLINE]
Free PMC Article
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