RNA



A test of the model to predict unusually stable RNA hairpin loop stability


TARAKA  DALE a1, RASHAAN  SMITH a1 and MARTIN J.  SERRA a1c1
a1 Department of Chemistry, Allegheny College, Meadville, Pennsylvania 16335, USA

Abstract

To investigate the accuracy of a model [Giese et al., 1998, Biochemistry 37:1094–1100 and Mathews et al., 1999, J Mol Biol 288:911–940] that predicts the stability of RNA hairpin loops, optical melting studies were conducted on sets of hairpins previously determined to have unusually stable thermodynamic parameters. Included were the tetraloops GNRA and UNCG (where N is any nucleotide and R is a purine), hexaloops with UU first mismatches, and the hairpin loop of the iron responsive element, CAGUGC. The experimental values for the GNRA loops are in excellent agreement ([Delta]G°37 within 0.2 kcal/mol and melting temperature (TM) within 4 °C) with the values predicted by the model. When the UNCG hairpin loops are treated as tetraloops, and a bonus of 0.8 kcal/mol included in the prediction to account for the extra stable first mismatch (UG), the measured and predicted values are also in good agreement ([Delta]G°37 within 0.7 kcal/mol and TM within 3 °C). Six hairpins with unusually stable UU first mismatches also gave good agreement with the predictions ([Delta]G°37 within 0.5 kcal/mol and TM within 8 °C), except for hairpins closed by wobble base pairs. For these hairpins, exclusion of the additional stabilization term for UU first mismatches improved the prediction ([Delta]G°37 within 0.1 kcal/mol and TM within 3 °C). Hairpins with the iron-responsive element loop were not predicted well by the model, as measured [Delta]G°37 values were at least 1 kcal/mol greater than predicted.

(Received December 1 1999)
(Revised January 1 2000)
(Accepted January 31 2000)


Key Words: nearest-neighbor parameters; RNA secondary structure.

Correspondence:
c1 Reprint requests to: Martin J. Serra, Department of Chemistry, Allegheny College, 520 N. Main St., Meadville, Pennsylvania 16335, USA; e-mail: mserra@alleg.edu.