RNA internal loops with tandem AG pairs: the structure of the 5'GAGU/3'UGAG loop can be dramatically different from others, including 5'AAGU/3'UGAA
Thermodynamic stabilities of 2 x 2 nucleotide tandem AG internal loops in RNA range from -1.3 to +3.4 kcal/mol at 37 degrees C and are not predicted well with a hydrogen-bonding model. To provide structural information to facilitate development of more sophisticated models for the sequence dependenc...
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Published in | Biochemistry (Easton) Vol. 49; no. 27; pp. 5817 - 5827 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
13.07.2010
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Subjects | |
Online Access | Get full text |
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Summary: | Thermodynamic stabilities of 2 x 2 nucleotide tandem AG internal loops in RNA range from -1.3 to +3.4 kcal/mol at 37 degrees C and are not predicted well with a hydrogen-bonding model. To provide structural information to facilitate development of more sophisticated models for the sequence dependence of stability, we report the NMR solution structures of five RNA duplexes: (rGACGAGCGUCA)(2), (rGACUAGAGUCA)(2), (rGACAAGUGUCA)(2), (rGGUAGGCCA)(2), and (rGACGAGUGUCA)(2). The structures of these duplexes are compared to that of the previously solved (rGGCAGGCC)(2) (Wu, M., SantaLucia, J., Jr., and Turner, D. H. (1997) Biochemistry 36, 4449-4460). For loops bounded by Watson-Crick pairs, the AG and Watson-Crick pairs are all head-to-head imino-paired (cis Watson-Crick/Watson-Crick). The structures suggest that the sequence-dependent stability may reflect non-hydrogen-bonding interactions. Of the two loops bounded by G-U pairs, only the 5'UAGG/3'GGAU loop adopts canonical UG wobble pairing (cis Watson-Crick/Watson-Crick), with AG pairs that are only weakly imino-paired. Strikingly, the 5'GAGU/3'UGAG loop has two distinct duplex conformations, the major of which has both guanosine residues (G4 and G6 in (rGACGAGUGUCA)(2)) in a syn glycosidic bond conformation and forming a sheared GG pair (G4-G6*, GG trans Watson-Crick/Hoogsteen), both uracils (U7 and U7*) flipped out of the helix, and an AA pair (A5-A5*) in a dynamic or stacked conformation. These structures provide benchmarks for computational investigations into interactions responsible for the unexpected differences in loop free energies and structure. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1520-4995 |
DOI: | 10.1021/bi100332r |