A capping-independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP.
A capping-independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP.
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MePCE 在稳定 7SK snRNA 和促进 7SK snRNP 组装方面具有不依赖加帽的功能。
DOI：
10.1093/nar/gkp977
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发表时间：
2010-01
影响因子：
14.9
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Xue Y;Yang Z;Chen R;Zhou Q
7SK snRNP代表了一个主要的活性库，其中P-TEFb是RNA聚合酶II延伸的通用转录因子，可以被撤回以促进基因表达，细胞生长和发育。在这种复合物中，7SK snRNA是协调关键蛋白质-蛋白质相互作用并维持P-TEFb处于非活性状态的中心支架。虽然7SK的稳定性直接影响体内活性P-TEFb的量，但关于其如何维持以及7SK甲基磷酸加帽酶MePCE和LARP 7（一种与7SK的3′-poly（U）相关的La相关蛋白）如何促成这一过程的了解相对较少。在这里，我们表明，7SK是由LARP 7的无MePCE加帽，并可能在其螯合成7SK snRNP之前的共转录方式。然而，在与7SK snRNP内的LARP 7相互作用后，MePCE失去其加帽活性，可能是由于LARP 7封闭其催化中心。尽管其在7SK snRNP中缺乏加帽活性，但MePCE显示出促进LARP 7 -7SK相互作用的不加帽功能，这反过来稳定了7SK并促进了稳定的MePCE-LARP 7 -7SK亚复合物的组装。我们的数据表明MePCE和LARP 7协同作用以稳定7SK并保持7SK snRNP的完整性。
The 7SK snRNP represents a major reservoir of activity where P-TEFb, a general transcription factor key for RNA polymerase II elongation, can be withdrawn to promote gene expression, cell growth and development. Within this complex, 7SK snRNA is a central scaffold that coordinates key protein–protein interactions and maintains P-TEFb in an inactive state. Although the stability of 7SK directly affects the amount of active P-TEFb in vivo, relatively little is known about how it is maintained and how the 7SK methylphosphate capping enzyme MePCE and LARP7, a La-related protein associated with the 3′-poly(U) of 7SK, contribute to this process. Here, we show that 7SK is capped by the LARP7-free MePCE and in probably a co-transcriptional manner prior to its sequestration into 7SK snRNP. However, upon interacting with LARP7 within 7SK snRNP, MePCE loses its capping activity, probably due to the occlusion of its catalytic center by LARP7. Despite its lack of capping activity in 7SK snRNP, MePCE displays a capping-independent function to promote the LARP7–7SK interaction, which in turn stabilizes 7SK and facilitates the assembly of a stable MePCE–LARP7–7SK subcomplex. Our data indicate that MePCE and LARP7 act cooperatively to stabilize 7SK and maintain the integrity of 7SK snRNP.
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