A NOVEL BASE-PAIRING INTERACTION BETWEEN U2 AND U6 SNRNAS SUGGESTS A MECHANISM FOR THE CATALYTIC ACTIVATION OF THE SPLICEOSOME
A NOVEL BASE-PAIRING INTERACTION BETWEEN U2 AND U6 SNRNAS SUGGESTS A MECHANISM FOR THE CATALYTIC ACTIVATION OF THE SPLICEOSOME
复制标题
DOI：
10.1016/0092-8674(92)90556-r
复制
发表时间：
1992-11-27
期刊：
影响因子：
64.5
通讯作者：
GUTHRIE, C
中科院分区：
文献类型：
--
作者：
MADHANI, HD;GUTHRIE, C
在mRNA剪接的化学步骤之前，U4和U6剪接体snRNA之间广泛的碱基配对相互作用被破坏。在这里，我们在酵母中使用突变分析来证明U6和U2 snRNA之间的保守碱基配对相互作用与U4-U6相互作用是互斥的。在这种新的配对中，U6中的保守序列与紧邻分支点识别区上游的U2中的序列相互作用。值得注意的是，在U6中的残基，因此可以与内含子底物并置包括那些先前已经提出的催化。当这种碱基配对结构发生突变时，剪接的第一步和第二步都受到抑制。这些观察结果，再加上U2-U6结构的高度保守性，使我们提出它可能是剪接体活性位点的一个组成部分。
Prior to the chemical steps of mRNA splicing, the extensive base-pairing interaction between the U4 and U6 spliceosomal snRNAs is disrupted. Here, we use a mutational analysis in yeast to demonstrate a conserved base-pairing interaction between the U6 and U2 snRNAs that is mutually exclusive with the U4-U6 interaction. In this novel pairing, conserved sequences in U6 interact with a sequence in U2 that is immediately upstream of the branch point recognition region. Remarkably, the residues in U6 that can be consequently juxtaposed with the intron substrate include those that have been proposed previously to be catalytic. Both the first and second steps of splicing are inhibited when this base-paired structure is mutated. These observations, together with the high conservation of the U2-U6 structure, lead us to propose that it might be a component of the spliceosomal active site.