An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition
An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition
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DOI：
10.1038/nsmb1149
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发表时间：
2006-10-01
影响因子：
16.8
通讯作者：
Lynch, Kristen W.
中科院分区：
文献类型：
--
作者：
House, Amy E.;Lynch, Kristen W.
前体信使RNA剪接是由剪接体催化的，剪接体是一种大分子复合物，在一个逐步的过程中组装。剪接体的动态特性表明，在组装途径的许多点上都有调控的潜力；然而，到目前为止，自然发生的剪接调节只被发现影响一小部分剪接体中间体。在这里，我们报道了抑制PTPRC（编码CD45）外显子4剪接的外显子剪接沉默子（ESS1）不通过抑制U1或U2小核核糖核蛋白（snRNPs）与剪接位点结合的典型机制起作用。相反，在外显子4上形成一个U1-， U2-和atp依赖的复合体，这是抑制向含有U4-U6-U5三snrnp的B复合体进展所必需的。这种抑制代表了剪接调控的一种新机制，并表明调控可能发生在剪接体组装途径的许多过渡中。
Precursor messenger RNA splicing is catalyzed by the spliceosome, a macromolecular complex that assembles in a stepwise process. The spliceosome's dynamic nature suggests the potential for regulation at numerous points along the assembly pathway; however, thus far, naturally occurring regulation of splicing has only been found to influence a small subset of spliceosomal intermediates. Here we report that the exonic splicing silencer (ESS1) that represses splicing of PTPRC (encoding CD45) exon 4 does not function by the typical mechanism of inhibiting binding of U1 or U2 small nuclear ribonucleoproteins (snRNPs) to the splice sites. Instead, a U1-, U2- and ATP-dependent complex forms across exon 4 that is required for inhibiting progression to the U4-U6-U5 tri-snRNP-containing B complex. Such inhibition represents a new mechanism for splicing regulation and suggests that regulation can probably occur at many of the transitions along the spliceosome assembly pathway.