Repositioning of the reaction intermediate within the catalytic center of the spliceosome
Repositioning of the reaction intermediate within the catalytic center of the spliceosome
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DOI：
10.1016/j.molcel.2006.01.017
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发表时间：
2006-02-17
期刊：
影响因子：
16
通讯作者：
Query, CC
中科院分区：
文献类型：
--
作者：
Konarska, MM;Vilardell, J;Query, CC
在pre-mRNA剪接的第一步（分支位点攻击5‘剪接位点）和第二步（5’外显子攻击3'剪接位点）之间需要剪接体内部的构象变化。然而，在这一过渡过程中，对反应底物的重新定位知之甚少。虽然5' SS通过与不变的U6 snRNA-ACAGAG位点配对来定位第一步，但我们证明这种配对相互作用必须被破坏才能过渡到第二步。我们提出，在第二步中，从催化中心去除分支结构与结合3' SS底物是竞争的。第一步和第二步底物在催化中心的相对占用的变化改变了两步剪接的效率，允许使用次优内含子序列，从而改变了底物的选择性。
Conformational change within the spliceosome is required between the first catalytic step of pre-mRNA splicing, when the branch site attacks the 5' splice site (SS), and the second step, when the 5' exon attacks the 3' SS. Little is known, however, about repositioning of the reaction substrates during this transition. Whereas the 5' SS is positioned for the first step by pairing with the invariant U6 snRNA-ACAGAG site, we demonstrate that this pairing interaction must be disrupted to allow transition to the second step. We propose that removal of the branch structure from the catalytic center is in competition with binding of the 3' SS substrate for the second step. Changes in the relative occupancy of first and second step substrates at the catalytic center alter efficiency of the two steps of splicing, allowing use of suboptimal intron sequences and thereby altering substrate selectivity.