Stability of RNA Hairpin Loops Closed by AU Base Pairs

• Published in: Biochemistry (Easton) 2004-09, Vol.43 (37), p.11813-11817
• Main Authors: Vecenie, Christopher J, Serra, Martin J
• Format: Article
• Language: English
• Subjects: Adenine - metabolism; Base Pairing; Base Sequence; Nucleic Acid Conformation; Nucleic Acid Denaturation; Oligoribonucleotides - genetics; Oligoribonucleotides - metabolism; RNA - chemistry; RNA - genetics; RNA Stability; Thermodynamics; Uracil - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi049954i

Thermodynamic parameters are reported for hairpin formation in 1 M NaCl by RNA sequence of the type GCAXUAAUYUGC, where XY is the set of 10 possible mismatch base pairs. A nearest-neighbor analysis of the data indicates that the free energy of loop formation at 37 °C varies from 3.2 to 5.0 kcal/mol. These results combined with the model previously developed [Dale et al. (2000) RNA 6, 608] allow improvements in the model to predict the stability of RNA hairpin loops:  ΔG°37L( n ) = ΔG°37i(n) + ΔG°37MM − 0.8 (if first mismatch is GA or UU) − 0.8 (if first mismatch is GG and loop is closed on 5‘ side by a purine). Here, ΔG°37i( n ) is the free energy for initiating a loop of n nucleotides, and ΔG°37MM is the free energy for the interaction of the first mismatch with the closing base pair. Hairpins with GG first mismatches were found to vary in stability depending upon the orientation of the closing base pair (5‘ or 3‘ purine relative to the loop). The model gives good agreement when tested against four naturally occurring hairpin sequences.