The multifunctional Ccr4-Not complex directly promotes transcription elongation
The multifunctional Ccr4-Not complex directly promotes transcription elongation
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DOI：
10.1101/gad.2020911
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发表时间：
2011-03-15
影响因子：
10.5
通讯作者：
Reese, Joseph C.
中科院分区：
文献类型：
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作者：
Kruk, Jennifer A.;Dutta, Arnob;Reese, Joseph C.
Ccr 4-Not复合物参与了mRNA代谢的多个步骤的控制;然而，其在转录中的功能仍然不明确。Ccr 4/Pop 2是主要的细胞质mRNA去腺苷酶的发现和mRNA加工体内Not蛋白的检测提出了关于Ccr 4-Not复合物在转录中的作用的问题。在这里，我们坚定地建立Ccr 4-Not作为RNA聚合酶II（RNAPII）的正延伸因子。Ccr 4-Not复合物以类似于RNAPII的转录依赖性方式靶向基因的编码区，并促进体内延伸。此外，Ccr 4-Not直接与延伸的RNAPII复合物相互作用，并刺激体外抑制的聚合酶的转录延伸。Ccr 4-Not可以使用与充分表征的延伸因子TFIIS不同的机制重新激活回溯RNAPII。虽然对于其与延伸复合物的相互作用不是必需的，但Ccr 4-Not与出现的转录物相互作用并以依赖于转录物长度的方式促进延伸，尽管这种相互作用对于其结合RNAPII不是必需的。我们的综合分析表明，Ccr 4-Not直接调节转录，并建议它这样做，通过促进恢复延长逮捕RNAPII时，它遇到体内转录块。
The Ccr4-Not complex has been implicated in the control of multiple steps of mRNA metabolism; however, its functions in transcription remain ambiguous. The discovery that Ccr4/Pop2 is the major cytoplasmic mRNA deadenylase and the detection of Not proteins within mRNA processing bodies have raised questions about the roles of the Ccr4-Not complex in transcription. Here we firmly establish Ccr4-Not as a positive elongation factor for RNA polymerase II (RNAPII). The Ccr4-Not complex is targeted to the coding region of genes in a transcription-dependent manner similar to RNAPII and promotes elongation in vivo. Furthermore, Ccr4-Not interacts directly with elongating RNAPII complexes and stimulates transcription elongation of arrested polymerase in vitro. Ccr4-Not can reactivate backtracked RNAPII using a mechanism different from that of the well-characterized elongation factor TFIIS. While not essential for its interaction with elongation complexes, Ccr4-Not interacts with the emerging transcript and promotes elongation in a manner dependent on transcript length, although this interaction is not required for it to bind RNAPII. Our comprehensive analysis shows that Ccr4-Not directly regulates transcription, and suggests it does so by promoting the resumption of elongation of arrested RNAPII when it encounters transcriptional blocks in vivo.