Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes.
Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes.
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集成剂复合物调节NELF介导的RNA聚合酶II暂停/释放和编码基因的加工性。
DOI：
10.1038/ncomms6531
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发表时间：
2014-11-20
影响因子：
16.6
通讯作者：
Benkirane, Monsef
中科院分区：
文献类型：
--
作者：
Stadelmayer, Bernd;Micas, Gael;Gamot, Adrien;Martin, Pascal;Malirat, Nathalie;Koval, Slavik;Raffel, Raoul;Sobhian, Bijan;Severac, Dany;Rialle, Stephanie;Parrinello, Hugues;Cuvier, Olivier;Benkirane, Monsef
RNA聚合酶II（RNAPII）在启动后不久暂停/终止是基因调控的标志。在这里，我们表明负延伸因子（NELF）与整合子复合物亚基（INTScom）、RNAPII和Spt 5相互作用。NELF和INTScom亚基之间的相互作用是RNA和DNA独立的。使用人类免疫缺陷病毒1型启动子和全基因组分析，我们证明，整合子亚基特异性控制NELF介导的RNAPII暂停/释放的编码基因。RNAPII暂停的强度由NELF相关的INTScom亚基的性质决定。有趣的是，除了控制RNAPII暂停释放INTS 11催化亚基的INTScom是RNAPII的持续合成所必需的。最后，INTScom靶基因富含人类免疫缺陷病毒1型反式激活反应元件/NELF结合元件和小核RNA生物合成所需的3'盒序列。揭示INTScom在调节RNAPII暂停释放和完成NELF靶基因mRNA合成中的这些意想不到的功能将有助于我们理解基因表达周期。 RNA聚合酶II（RNAPII）在转录起始位点的停顿是基因转录调控的重要因素。在这里，作者暗示整合子复合物是RNAPII暂停释放和完成负延伸因子靶基因亚组mRNA合成的调节剂。
RNA polymerase II (RNAPII) pausing/termination shortly after initiation is a hallmark of gene regulation. Here, we show that negative elongation factor (NELF) interacts with Integrator complex subunits (INTScom), RNAPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both human immunodeficiency virus type 1 promoter and genome-wide analyses, we demonstrate that Integrator subunits specifically control NELF-mediated RNAPII pause/release at coding genes. The strength of RNAPII pausing is determined by the nature of the NELF-associated INTScom subunits. Interestingly, in addition to controlling RNAPII pause-release INTS11 catalytic subunit of the INTScom is required for RNAPII processivity. Finally, INTScom target genes are enriched in human immunodeficiency virus type 1 transactivation response element/NELF binding element and in a 3' box sequence required for small nuclear RNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pause-release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle. RNA polymerase II (RNAPII) pausing at transcriptional start sites is an important element of gene transcription regulation. Here, the authors implicate the Integrator complex as a regulator of RNAPII pause-release and completion of mRNA synthesis at a subset of the negative elongation factor target genes.
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影响因子：
64.5
作者：
Wagschal A;Rousset E;Basavarajaiah P;Contreras X;Harwig A;Laurent-Chabalier S;Nakamura M;Chen X;Zhang K;Meziane O;Boyer F;Parrinello H;Berkhout B;Terzian C;Benkirane M;Kiernan R
通讯作者：
Kiernan R
影响因子：
7.5
作者：
Bres, Vanessa;Yoh, Sunnie M.;Jones, Katherine A.
通讯作者：
Jones, Katherine A.
DOI：
10.1126/science.1145989
发表时间：
2007-12-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egloff S;O'Reilly D;Chapman RD;Taylor A;Tanzhaus K;Pitts L;Eick D;Murphy S
通讯作者：
Murphy S
影响因子：
64.5
作者：
Gilchrist DA;Dos Santos G;Fargo DC;Xie B;Gao Y;Li L;Adelman K
通讯作者：
Adelman K
影响因子：
11.4
作者：
HERNANDEZ, N
通讯作者：
HERNANDEZ, N