A conformational rearrangement in the spliceosome sets the stage for prp22-dependent mRNA release
A conformational rearrangement in the spliceosome sets the stage for prp22-dependent mRNA release
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DOI：
10.1016/j.molcel.2008.05.003
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发表时间：
2008-06-20
期刊：
影响因子：
16
通讯作者：
Schwer, Beate
中科院分区：
文献类型：
--
作者：
Schwer, Beate
前mRNA剪接的一个重要步骤是从剪接体中释放mRNA产物。DEAH盒RNA解旋酶Prp22通过重塑涉及U5 snRNP的剪接体内的接触来催化mRNA释放。剪接体的拆卸需要在3'剪接位点下游有超过13个核糖核苷酸的片段。我在这里通过位点特异性交联和RNase H保护表明，在mRNA释放之前，Prp22与外显子-外显子连接处下游的mRNA相互作用。这些发现支持了Prp22催化的mRNA从剪接体释放的模型，其中伴随第二次酯交换步骤的重排将Prp22沉积在外显子-外显子连接下游的mRNA上。与靶RNA结合后，3‘-> 5’解旋酶破坏mRNA/U5 snRNP的接触，从而将mRNA从剪接体中解放出来。
An essential step in pre-mRNA splicing is the release of the mRNA product from the spliceosome. The DEAH box RNA helicase Prp22 catalyzes mRNA release by remodeling contacts within the spliceosome that involve the U5 snRNP. Spliceosome disassembly requires a segment of more than 13 ribonucleotides downstream of the 3' splice site. I show here by site-specific crosslinking and RNase H protection that Prp22 interacts with the mRNA downstream of the exon-exon junction prior to mRNA release. The findings support a model for Prp22-catalyzed mRNA release from the spliceosome wherein a rearrangement that accompanies the second transesterification step deposits Prp22 on the mRNA downstream of the exon-exon junction. Bound to its target RNA, the 3'-> 5' helicase acts to disrupt mRNA/U5 snRNP contacts, thereby liberating the mRNA from the spliceosome.