Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression.
Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression.
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高渗胁迫改变了RNA聚合酶II的相互作用体，并诱导了直读转录，尽管存在广泛的转录抑制。
DOI：
10.1016/j.molcel.2020.12.002
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发表时间：
2021-02-04
期刊：
影响因子：
16
通讯作者：
Steitz JA
中科院分区：
文献类型：
--
作者：
Rosa-Mercado NA;Zimmer JT;Apostolidi M;Rinehart J;Simon MD;Steitz JA
应激诱导的通读转录导致含有转录物的基因下游(DOG)的合成。在细胞应激过程中狗的形成机制尚不清楚。利用TT-TIMELAPSE-SEQ在狗诱导人类细胞系过程中的新生转录图谱显示了对高渗应激的广泛转录抑制。然而，狗的产生与其上游基因的转录水平无关。CHIP-SEQ证实，应激诱导的RNA聚合酶(POL)II的重新分布与基因的转录输出相关。用质谱仪观察了应激诱导的POL II相互作用组的变化。虽然某些切割和多聚腺苷化因子仍然与Pol II相关，但在应激条件下，整合子复合体亚基从Pol II解离，导致DNA上整合子的全基因组丢失。使用siRNAs耗尽整合子的催化亚单位会诱导数百个通读转录本，其父母基因部分与应激诱导的狗的转录本重叠。我们的结果为深入了解狗生产的潜在机制以及整合者的活动如何影响狗的转录提供了见解。Rosa-Mercado等人。报告指出，高渗应激在人类细胞中引起广泛的转录抑制，然而，无论其上游基因的转录反应如何，基因下游转录物(狗)都会出现。POL II和整合子之间的相互作用被高张和整合子核酸酶敲除而中断，从而导致犬的生产。
Stress-induced readthrough transcription results in the synthesis of downstream-of-gene (DoG) containing transcripts. The mechanisms underlying DoG formation during cellular stress remain unknown. Nascent transcription profiles during DoG induction in human cell lines using TT-TimeLapse-seq revealed widespread transcriptional repression upon hyperosmotic stress. Yet, DoGs are produced regardless of the transcriptional level of their upstream genes. ChIP-seq confirmed that stress-induced redistribution of RNA Polymerase (Pol) II correlates with the transcriptional output of genes. Stress-induced alterations in the Pol II interactome are observed by mass spectrometry. While certain cleavage and polyadenylation factors remained Pol II-associated, Integrator complex subunits dissociate from Pol II under stress leading to a genome-wide loss of Integrator on DNA. Depleting the catalytic subunit of the Integrator using siRNAs induces hundreds of readthrough transcripts, whose parental genes partially overlap those of stress-induced DoGs. Our results provide insights into the mechanisms underlying DoG production and how Integrator activity influences DoG transcription. Rosa-Mercado et al. report that hyperosmotic stress causes widespread transcriptional repression in human cells, yet downstream-of-gene transcripts (DoGs) arise regardless of the transcriptional response of their upstream genes. Interactions between Pol II and Integrator are disrupted by hypertonicity and knockdown of the Integrator nuclease leads to DoG production.
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影响因子：
10.5
作者：
Eaton JD;Davidson L;Bauer DLV;Natsume T;Kanemaki MT;West S
通讯作者：
West S
使用有效和可逆的共价化学跟踪不同的RNA群体。
影响因子：
16
作者：
Duffy EE;Rutenberg-Schoenberg M;Stark CD;Kitchen RR;Gerstein MB;Simon MD
通讯作者：
Simon MD
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
10.5
作者：
Boutz PL;Bhutkar A;Sharp PA
通讯作者：
Sharp PA
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A