PMID- 19476351
OWN - NLM
STAT- MEDLINE
DCOM- 20090804
LR  - 20090617
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Linking)
VI  - 131
IP  - 24
DP  - 2009 Jun 24
TI  - Contribution of the closing base pair to exceptional stability in RNA tetraloops: 
      roles for molecular mimicry and electrostatic factors.
PG  - 8474-84
LID - 10.1021/ja900065e [doi]
AB  - Hairpins are common RNA secondary structures that play multiple roles in nature. 
      Tetraloops are the most frequent RNA hairpin loops and are often phylogenetically 
      conserved. For both the UNCG and GNRA families, CG closing base pairs (cbps) 
      confer exceptional thermodynamic stability but the molecular basis for this has 
      remained unclear. We propose that, despite having very different overall folds, 
      these two tetraloop families achieve stability by presenting the same 
      functionalities to the major groove edge of the CG cbp. Thermodynamic 
      contributions of this molecular mimicry were investigated using substitutions at 
      the nucleobase and functional group levels. By either interrupting or deleting 
      loop-cbp electrostatic interactions, which were identified by solving the 
      nonlinear Poisson-Boltzmann (NLPB) equation, stability changed in a manner 
      consistent with molecular mimicry. We also observed a linear relationship between 
      DeltaG(o)(37) and log[Na(+)] for both families, and loops with a CG cbp had a 
      decreased dependence of stability on salt. NLPB calculations revealed that, for 
      both UUCG and GAAA tetraloops, the GC cbp form has a higher surface charge 
      density, although it arises from changes in loop compaction for UUCG and changes 
      in loop configuration for GAAA. Higher surface charge density leads to stronger 
      interactions of GC cbp loops with solvent and salt, which explains the 
      correlation between experimental and calculated trends of free energy with salt. 
      Molecular mimicry as evidenced in these two stable but otherwise unrelated 
      tetraloops may underlie common functional roles in other RNA and DNA motifs.
FAU - Blose, Joshua M
AU  - Blose JM
AD  - Department of Chemistry, The Pennsylvania State University, University Park, 
      Pennsylvania 16802, USA.
FAU - Proctor, David J
AU  - Proctor DJ
FAU - Veeraraghavan, Narayanan
AU  - Veeraraghavan N
FAU - Misra, Vinod K
AU  - Misra VK
FAU - Bevilacqua, Philip C
AU  - Bevilacqua PC
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Base Pairing
MH  - Models, Molecular
MH  - Molecular Mimicry
MH  - Nucleic Acid Conformation
MH  - RNA/*chemistry
MH  - Static Electricity
MH  - Thermodynamics
MH  - Transition Temperature
EDAT- 2009/05/30 09:00
MHDA- 2009/08/06 09:00
CRDT- 2009/05/30 09:00
PHST- 2009/05/30 09:00 [entrez]
PHST- 2009/05/30 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
AID - 10.1021/ja900065e [doi]
PST - ppublish
SO  - J Am Chem Soc. 2009 Jun 24;131(24):8474-84. doi: 10.1021/ja900065e.