Thermodynamic characterization of single mismatches found in naturally occurring RNA

被引:47
作者
Davis, Amber R. [1 ]
Znosko, Brent M. [1 ]
机构
[1] St Louis Univ, Dept Chem, St Louis, MO 63103 USA
关键词
D O I
10.1021/bi701311c
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Many naturally occurring RNA structures contain single mismatches. However, the algorithms currently used to predict RNA structure from sequence rely on a minimal set of data for single mismatches, most of which occur rather infrequently in nature. As a result, several approximations and assumptions are used to predict the stability of RNA duplexes containing the most common single mismatches. Therefore, the relative frequency of single mismatches was determined by compiling and searching a database of 955 RNA secondary structures. Thermodynamic parameters for duplex formation, derived from optical melting experiments, are reported for 28 oligoribonucleotides containing frequently occurring single mismatches. These data were then combined with previous data to construct a dataset of 64 single mismatches, including the 30 most common in the database. Because of this increase in experimental thermodynamic parameters for single mismatches that occur frequently in nature, more accurate free energy calculations have resulted. To improve the prediction of the thermodynamic parameters for duplexes containing single mismatches that have not been experimentally measured, single mismatch-specific nearest neighbor parameters were derived. The free energy of an RNA duplex containing a single mismatch that has not been thermodynamically characterized can be calculated by: Delta G degrees(37,single mismatch) = Delta G degrees 3(7,mismatch nt) + Delta G degrees(37,mismatch-NN interaction) + Delta G degrees(37,AU/GU). Here, Delta G degrees(37,mismatch) is -0.4, -2.1, and -0.3 kcal/mol for A center dot G, G center dot G, and U center dot U mismatches, respectively; AG037,mismatch-NN interaction is 0.7, -0.5, 0.4, -0.4, and -1.0 kcal/mol for 5'YRR3'/3'RRY5', 5'RYY3'/3'YYR5', 5'YYR3/3'RYY5', 5'YRY3'/3'RYR5', and 5'RRY3'/3'YYR5' mismatch-nearest neighbor combinations, respectively, when A and G are categorized as purines (R) and C and U are categorized as pyrimidines (Y); and Delta G degrees(37,AU/GU) is a penalty of 1.2 kcal/mol for replacing a G-C base pair with either an A-U or G-U base pair. Similar predictive models were also derived for Delta H degrees (single) (mismatch) and Delta S degrees(sinngle) (mismatch). These new predictive models, in conjunction with the reported thermodynamics for frequently occurring single mismatches, should allow for more accurate calculations of the free energy of RNA duplexes containing single mismatches and, furthermore, allow for improved prediction of secondary structure from sequence.
引用
收藏
页码:13425 / 13436
页数:12
相关论文
共 48 条
[21]   Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure [J].
Mathews, DH ;
Disney, MD ;
Childs, JL ;
Schroeder, SJ ;
Zuker, M ;
Turner, DH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (19) :7287-7292
[22]   Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure [J].
Mathews, DH ;
Sabina, J ;
Zuker, M ;
Turner, DH .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 288 (05) :911-940
[23]   Investigation of the structural basis for thermodynamic stabilities of tandem GU mismatches: Solution structure of (rGAGGUCUC)(2) by two-dimensional NMR and simulated annealing [J].
McDowell, JA ;
Turner, DH .
BIOCHEMISTRY, 1996, 35 (45) :14077-14089
[24]  
MCDOWELL JA, 1995, RNA CALCULATIONS VER
[25]   COMPARATIVE AND FUNCTIONAL-ANATOMY OF GROUP-II CATALYTIC INTRONS - A REVIEW [J].
MICHEL, F ;
UMESONO, K ;
OZEKI, H .
GENE, 1989, 82 (01) :5-30
[26]   THERMODYNAMIC STUDY OF INTERNAL LOOPS IN OLIGORIBONUCLEOTIDES - SYMMETRICAL LOOPS ARE MORE STABLE THAN ASYMMETRIC LOOPS [J].
PERITZ, AE ;
KIERZEK, R ;
SUGIMOTO, N ;
TURNER, DH .
BIOCHEMISTRY, 1991, 30 (26) :6428-6436
[27]   BASE-STACKING AND BASE-PAIRING CONTRIBUTIONS TO HELIX STABILITY - THERMODYNAMICS OF DOUBLE-HELIX FORMATION WITH CCGG, CCGGP, CCGGAP, ACCGGP, CCGGUP, AND ACCGGUP [J].
PETERSHEIM, M ;
TURNER, DH .
BIOCHEMISTRY, 1983, 22 (02) :256-263
[28]   Structures of CUG repeats in RNA - Potential implications for human genetic diseases [J].
Pinheiro, P ;
Scarlett, G ;
Rodger, A ;
Rodger, PM ;
Murray, A ;
Brown, T ;
Newbury, SF ;
McClellan, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (38) :35183-35190
[29]   Myotonic dystrophy: RNA pathogenesis comes into focus [J].
Ranum, LPW ;
Day, JW .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (05) :793-804
[30]   PROCESSING OF MESSENGER-RNA BY RIBONUCLEASE-III REGULATES EXPRESSION OF GENE 1.2 OF BACTERIOPHAGE-T7 [J].
SAITO, H ;
RICHARDSON, CC .
CELL, 1981, 27 (03) :533-542