Thermodynamic study of internal loops in oligoribonucleotides: symmetric loops are more stable than asymmetric loops

Abstract

Thermodynamic parameters for internal loops of unpaired adenosines in oligoribonucleotides have been measured by optical melting studies. Comparisons are made between helices containing symmetric and asymmetric loops. Asymmetric loops destabilize a helix more than symmetric loops. The differences in free energy between symmetric and asymmetric loops are roughly half the magnitude suggested from a study of parameters required to give accurate predictions of RNA secondary structure [Papanicolaou, C., Gouy, M., & Ninio, J. (1984) Nucleic Acids Res. 12, 31-44]. Circular dichroism spectra indicate no major structural difference between helices containing symmetric and asymmetric loops. The measured sequence dependence of internal loop stability is not consistent with approximations used in current algorithms for predicting RNA secondary structure.

A Kinetic and Thermodynamic Framework for the Hammerhead Ribozyme Reaction

“…The difference in stability between predicted and observed values, AAG = 6.7 kcal/mol, might then reflect the destabilizing thermodynamic contribution of the "single-stranded" core nucleotides. This value is similar to the destabilization of a complementary RNA helix containing a bulge loop of three nucleotides (AGO -6.4 kcal/ mol) (Longfellow et al, 1990) or an extremely asymmetric internal loop with six unpaired A nucleotides (AGO = 4.6 kcal/mol) (Peritz et al, 1991). We have performed the same calculation for a different hammerhead (HH8) for which AG* was measured to be-10 kcal/mol (Fedor & Uhlenbeck, 1992).…”

Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure

“…Internal loop free energy parameters are revised on the basis of recent measurements (58)(59)(60)(61) and the previously assembled database (8,45,46,(62)(63)(64)(65)(66)(67)(68)(69). In the program described here, measured values are used when available for 1 ϫ 1, 1 ϫ 2, and 2 ϫ 2 internal loops, but approximations are used for most internal loops.…”

“…The ⌬G°3 7 GG(2 ϫ 2) term (Ϫ1.3 Ϯ 0.2 kcal͞mol) is applied to loops with a GG pair adjacent to an AA or any noncanonical pair with a pyrimidine. Values for ⌬ p and ⌬G°37 GG were obtained by linear regression on the 2 ϫ 2 loop database (8,58,62,64,65,68). Other internal loops are approximated by ⌬G°3 7 loop(n) ϭ ⌬G°37 loop initiation(n) ϩ ⌬G°37 AU͞GUϩ ͉n1 Ϫ n2͉ ⌬G°3 7 asym ϩ ⌬G°37 first noncanonical pairs(except for 1 ϫ (n Ϫ 1) for n Ͼ 3).…”

“…For example, an isoenergetic bulged C in 5ЈUGU͞3ЈACCA can occur in two positions. ⌬G°3 7 (special C bulge), Ϫ0.9 Ϯ 0.3 kcal (1 cal ϭ 4.18 J)͞mol, is an empirical bonus applied to bulged C residues adjacent to at least one C. The ⌬G°3 7 bulge initiation for single nucleotide bulges is 3.81 Ϯ 0.08 kcal͞mol.Internal loop free energy parameters are revised on the basis of recent measurements (58-61) and the previously assembled database (8,45,46,(62)(63)(64)(65)(66)(67)(68)(69)). In the program described here, measured values are used when available for 1 ϫ 1, 1 ϫ 2, and Abbreviation: RT, reverse transcription.…”

Computational approaches for RNA energy parameter estimation

“…Secondly, we collected a thermodynamic set denoted by T-Full that contains data from 1291 optical melting experiments, published in 53 research articles Sugimoto et al 1986Sugimoto et al , 1987Uhlenbeck 1988, 1989;Longfellow et al 1990;SantaLucia et al 1990SantaLucia et al , 1991aAntao et al 1991;He et al 1991;Peritz et al 1991;Antao and Tinoco 1992;Serra et al 1993Serra et al , 1994Serra et al , 1997Serra et al , 2004Walter et al 1994;Morse and Draper 1995;Wu et al 1995;Laing and Hall 1996;McDowell and Turner 1996;McDowell et al 1997;Schroeder et al 1996Schroeder et al , 2003Xia et al 1997Xia et al , 1998Giese et al 1998;Kierzek et al 1999;Meroueh and Chow 1999;Dale et al 2000;Turner 2000, 2001;Burkard et al 2001;Diamond et al 2001;Mathews and Turner 2002;Proctor et al 2002;Znosko et al 2002Znosko et al , 2004Chen et al 2004Chen et al , 2005Mathews et al 2004;Vecenie and Serra 2004;Bourdélat-Parks and Wartell 2005;…”