Crosstalk between mRNA 3′ End Processing and Transcription Initiation
Crosstalk between mRNA 3′ End Processing and Transcription Initiation
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DOI：
10.1016/j.molcel.2010.10.012
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发表时间：
2010-11-12
期刊：
影响因子：
16
通讯作者：
Jensen, Torben Heick
中科院分区：
文献类型：
--
作者：
Mapendano, Christophe K.;Lykke-Andersen, Soren;Jensen, Torben Heick
转录和mRNA成熟是相互依赖的事件。虽然在同一轮转录中这些过程之间的刺激连接被很好地描述，但单独的转录周期之间的功能耦合仍然难以捉摸。比较单拷贝整合β-珠蛋白基因变体的时间分辨转录谱，我们证明了多聚腺苷酸化位点突变降低了相同基因的转录起始。在3'端加工和转录终止因子PCF 11耗尽后，内源基因表现出相似的表型。参与多聚腺苷酸化位点突变的转录单位的通读RNA聚合酶II（RNAPII）隔离转录起始/延伸因子TBP、TFIIB和CDK 9，导致它们在启动子处耗尽。此外，高水平的TBP和TFIIB出现在基因体内，并且Ser 2-磷酸化的RNAPII在启动子处积累。我们的数据表明，3'端的形成刺激转录起始，并建议，协调循环的因素从基因终止子回到启动子是必不可少的持续转录。
Transcription and mRNA maturation are interdependent events. Although stimulatory connections between these processes within the same round of transcription are well described, functional coupling between separate transcription cycles remains elusive. Comparing time-resolved transcription profiles of single-copy integrated beta-globin gene variants, we demonstrate that a polyadenylation site mutation decreases transcription initiation of the same gene. Upon depletion of the 3' end processing and transcription termination factor PCF11, endogenous genes exhibit a similar phenotype. Readthrough RNA polymerase II (RNAPII) engaged on polyadenylation site-mutated transcription units sequester the transcription initiation/elongation factors TBP, TFIIB and CDK9, leading to their depletion at the promoter. Additionally, high levels of TBP and TFIIB appear inside the gene body, and Ser2-phosphorylated RNAPII accumulates at the promoter. Our data demonstrate that 3' end formation stimulates transcription initiation and suggest that coordinated recycling of factors from a gene terminator back to the promoter is essential for sustaining continued transcription.