Hinge stiffness is a barrier to RNA folding.
Cation-mediated RNA folding from extended to compact, biologically active conformations relies on a temporal balance of forces. The Mg2 +-mediated folding of the Tetrahymena thermophila ribozyme is characterized by rapid nonspecific collapse followed by tertiary-contact-induced compaction. This article focuses on an autonomously folding portion of the Tetrahymena ribozyme, its P4-P6 domain, in order to probe one facet of the rapid collapse: chain flexibility. The time evolution of P4-P6 folding was followed by global and local measures as a function of Mg2 + concentration. While all concentrations of Mg2 + studied are sufficient to screen the charge on the helices, the rates of compaction and tertiary contact formation diverge as the concentration of Mg2 + increases; collapse is greatly accelerated by Mg2 +, while tertiary contact formation is not. These studies highlight the importance of chain stiffness to RNA folding; at 10 mM Mg2 +, a stiff hinge limits the rate of P4-P6 folding. At higher magnesium concentrations, the rate-limiting step shifts from hinge bending to tertiary contact formati
Schlatterer
Jörg C
JC
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Kwok
Lisa W
LW
Lamb
Jessica S
JS
Park
Hye Yoon
HY
Andresen
Kurt
K
Brenowitz
Michael
M
Pollack
Lois
L
D000818:Animals; D001483:Base Sequence; D017665:Hydroxyl Radical / Q000737:chemistry; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009994:Osmolar Concentration; D012313:RNA / Q000737:chemistry*; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics; D016053:RNA, Protozoan / Q000737:chemistry / Q000235:genetics; D053838:Scattering, Small Angle; D016808:Tetrahymena thermophila / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D014961:X-Ray Diffraction
D016337:RNA, Catalytic; D016053:RNA, Protozoan; D017665:Hydroxyl Radical; D012313:RNA; D008274:Magnesium