Treiber D K, Rook M S, Zarrinkar P P, Williamson J R
Department of Molecular Biology, MB33, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 1998 Mar 20;279(5358):1943-6. doi: 10.1126/science.279.5358.1943.
In the magnesium ion-dependent folding of the Tetrahymena ribozyme, a kinetic intermediate accumulates in which the P4-P6 domain is formed, but the P3-P7 domain is not. The kinetic barriers to P3-P7 formation were investigated with the use of in vitro selection to identify mutant RNA molecules in which the folding rate of the P3-P7 domain was increased. The critical mutations disrupt native tertiary interactions within the P4-P6 domain and increase the rate of P3-P7 formation by destabilizing a kinetically trapped intermediate. Hence, kinetic traps stabilized by native interactions, and not simply by mispaired nonnative structures, can present a substantial barrier to RNA folding.
在嗜热四膜虫核酶的镁离子依赖性折叠过程中，会积累一种动力学中间体，其中P4 - P6结构域已形成，但P3 - P7结构域未形成。利用体外筛选来研究P3 - P7形成的动力学障碍，以鉴定P3 - P7结构域折叠速率增加的突变RNA分子。关键突变破坏了P4 - P6结构域内的天然三级相互作用，并通过使动力学捕获的中间体不稳定来提高P3 - P7形成的速率。因此，由天然相互作用而非简单地由错配的非天然结构稳定的动力学陷阱，可能会对RNA折叠构成实质性障碍。
