Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step
Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step
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DOI：
10.1128/jvi.75.9.4376-4385.2001
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Clements, JB
中科院分区：
文献类型：
--
作者：
Bryant, HE;Wadd, SE;Clements, JB
多功能单纯疱疹病毒1型（HSV-1）蛋白IE63（ICP 27）与必需的前mRNA剪接因子剪接体相关蛋白145（SAP 145）相互作用，并且在感染的细胞中IE63和SAP 145共定位。使用感染IE63病毒突变体的细胞提取物，这种相互作用被完全减少或消除，IE63 RH和Sm同源结构域中的突变，不表现出宿主关闭或抑制剪接。在IE63的存在下，体外剪接在第一催化步骤之前被抑制，并且剪接期间形成的B/C复合物的迁移率升高并且强度降低。在剪接提取物的作用下，IE 63和SAP 145均与B/C复合物共迁移，表明它们在该复合物内相互作用以抑制B/C复合物的形成或转化。剪接的抑制可能促进病毒或细胞转录物的输出，可能通过IE63的其他蛋白质伴侣。这些数据为IE63如何影响HSV-I感染期间的前mRNA加工提供了重要的新见解。
The multifunctional herpes simplex virus type 1 (HSV-1) protein IE63 (ICP27) interacts with the essential pre-mRNA splicing factor, spliceosome-associated protein 145 (SAP145), and in infected cells IE63 and SAP145 colocalize. This interaction was reduced or abrogated completely using extracts from cells infected with IE63 viral mutants, with mutations in IE63 RH and Sm homology domains, which do not exhibit host shutoff or inhibit splicing. In the presence of IE63, splicing in vitro was inhibited prior to the first catalytic step and the B/C complex formed during splicing was shifted up in mobility and reduced in intensity. With the use of splicing extracts, IE63 and SAP145 both comigrated with the B/C complex, suggesting that they interact within this complex to inhibit B/C complex formation or conversion. The inhibition of splicing may facilitate the export of viral or cellular transcripts, possibly via other protein partners of IE63, These data provide important new insights into how IE63 influences pre-mRNA processing during HSV-I infection.