Stepwise conversion of a mesophilic to a thermophilic ribozyme.
A fundamental question in RNA folding is the mechanism of thermodynamic stability. We investigated the equilibrium folding of a series of sequence variants in which one to three motifs of a 255-nucleotide mesophilic ribozyme were substituted with the corresponding motifs from its thermophilic homologue. Substitution of three crucial motifs individually or in groups results in a continual increase in the stability and folding cooperativity in a stepwise fashion. We find an unexpected relationship between stability and folding cooperativity. Without changing the folding cooperativity, RNAs having a similar native structure can only achieve moderate change in stability and likewise, without changing stability, RNAs having a similar native structure can only achieve moderate change in folding cooperativity. This intricate relationship must be included in the predictions of tertiary RNA stability.
Fang
X-W
XW
Department of Biochemistry and Molecular Biology, University of Chicago, 920 E 58th Street, Chicago, IL 60637, USA.
Srividya
N
N
Golden
B L
BL
Sosnick
T R
TR
Pan
T
T
D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D001411:Geobacillus stearothermophilus / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
D016337:RNA, Catalytic