The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response
The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response
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DOI：
10.1016/s0092-8674(00)80369-4
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发表时间：
1997-09-19
期刊：
影响因子：
64.5
通讯作者：
Walter, P
中科院分区：
文献类型：
--
作者：
Sidrauski, C;Walter, P
内质网（ER）通过未折叠蛋白反应（UPR）与细胞核通讯，该反应感知未折叠蛋白在ER腔中的积累，并导致编码ER驻留伴侣的基因的转录增加。作为该信号通路中的关键调节步骤，编码UPR特异性转录因子Hac 1 p的mRNA通过需要tRNA连接酶而不是剪接体的独特机制进行剪接。剪接在Ire 1 p激活后开始，Ire 1 p是一种位于ER和/或内核膜中的跨膜激酶。我们表明，Ire 1 p是一种双功能酶：除了是一种激酶，它是一个位点特异性内切核糖核酸酶，专门在两个剪接点切割HAC 1 mRNA。加入纯化的tRNA连接酶完成剪接，因此我们从纯化的组分在体外重建了HAC 1 mRNA剪接。
The endoplasmic reticulum (ER) communicates with the nucleus through the unfolded protein response (UPR), which senses accumulation of unfolded proteins in the ER lumen and leads to increased transcription of genes encoding ER-resident chaperones. As a key regulatory step in this signaling pathway, the mRNA encoding the UPR-specific transcription factor Hac1p becomes spliced by a unique mechanism that requires tRNA ligase but not the spliceosome. Splicing is initiated upon activation of Ire1p, a transmembrane kinase that lies in the ER and/or inner nuclear membrane. We show that Ire1p is a bifunctional enzyme: in addition to being a kinase, it is a site-specific endoribonuclease that cleaves HAC1 mRNA specifically at both splice junctions. The addition of purified tRNA ligase completes splicing; we therefore have reconstituted HAC1 mRNA splicing in vitro from purified components.