德国哥廷根生物物理化学MPI Reinhard Lührmann和Holger Stark研究组合作的研究，揭示了剪接体激活过程中蛋白质介导的RNA活性位点U2/U6的折叠机制。该项研究成果发表在2020年11月26日出版的《科学》上。
研究人员解析了之前报道的两个人类前-Bact复合物分辨率为3.9-4.2Å的冷冻电镜结构。该结构阐明了激活过程中发生的众多蛋白质交换顺序、相互排斥作用（确保形成U2/U6催化RNA所需的核糖核蛋白正确重排顺序）以及后续的逐步折叠途径。与成熟Bact复合物的结构比较揭示了支架蛋白PRP8的构象变化促进U2/U6催化RNA最终3D折叠的分子机制。
研究人员表示，剪接体活化涉及广泛的蛋白质和RNA重排，从而形成具有催化活性的U2/U6 RNA结构。 目前，关于U2/U6 RNA结构的组装途径以及蛋白质协助其正确折叠的机制知之甚少。
附：英文原文
Title: Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation
Author: Cole Townsend, Majety N. Leelaram, Dmitry E. Agafonov, Olexandr Dybkov, Cindy L. Will, Karl Bertram, Henning Urlaub, Berthold Kastner, Holger Stark, Reinhard Lührmann
Issue&Volume: 2020/11/26
Abstract: AbstractSpliceosome activation involves extensive protein and RNA rearrangements that lead to formation of a catalytically-active U2/U6 RNA structure. At present, little is known about the assembly pathway of the latter and the mechanism whereby proteins aid its proper folding. Here we report the cryo-electron microscopy structures of two human pre-Bact complexes at core resolutions of 3.9-4.2 . These structures elucidate the order of the numerous protein exchanges that occur during activation, the mutually-exclusive interactions that ensure the correct order of ribonucleoprotein rearrangements needed to form the U2/U6 catalytic RNA, and the stepwise folding pathway of the latter. Structural comparisons with mature Bact complexes reveal the molecular mechanism whereby a conformational change in the scaffold protein PRP8 facilitates final 3D folding of the U2/U6 catalytic RNA.
DOI: 10.1126/science.abc3753
Source: https://science.sciencemag.org/content/early/2020/11/24/science.abc3753