CHAPERONE-MEDIATED FOLDING OF A GROUP I INTRON RNA MONITORED BY SAXS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 许多功能性RNA在抗衡离子存在下折叠成离散的天然结构。这其中的关键一步 折叠过程是一个整体压缩，这已经成功地通过小角X射线散射（SAXS）监测了几种RNA（1-6）。对于充分研究的四膜虫I组核酶，这种全局压缩过程以约100 ms的时间常数发生，而由于形成至少两种错误折叠构象，完全折叠到天然状态要慢几个数量级（3，7，8）。CYT-19是一种DEAD盒ATP酶蛋白，在体内在I组内含子和其他RNA的折叠中起作用。我们最近使用核酶活性作为天然折叠的读数，以表明CYT-19通过非特异性地促进部分解折叠来加速从这些错误折叠的中间体之一的折叠（9，10）。这种非特异性解折叠允许更稳定的天然结构积累。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Many functional RNAs fold in the presence of counterions to discrete native structures. A crucial step in this folding process is a global compaction, which has been monitored successfully by small angle x-ray scattering (SAXS) for several RNAs (1-6). For the well-studied Tetrahymena group I ribozyme, this global compaction process occurs with a time constant of ~100 ms, whereas complete folding to the native state is slower by several orders of magnitude due to the formation of at least two misfolded conformations (3, 7, 8). CYT-19 is a DEAD-box ATPase protein that functions in vivo in folding of group I introns and other RNAs. We have recently used ribozyme activity as a readout for native folding to show that CYT-19 accelerates folding from one of these misfolded intermediates by non-specifically promoting partial unfolding (9, 10). This non-specific unfolding allows the more stable native structure to accumulate.