Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis.
Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis.
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DOI：
10.7554/elife.58342
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发表时间：
2021-06-04
期刊：
影响因子：
7.7
通讯作者：
Glaunsinger BA
中科院分区：
文献类型：
--
作者：
Duncan-Lewis C;Hartenian E;King V;Glaunsinger BA
RNA丰度通常对衰变和合成速率的扰动敏感，但RNA聚合酶II转录和细胞质mRNA降解之间的串扰往往导致基因表达的补偿性变化。在这里，我们发现，广泛的mRNA衰减在早期细胞凋亡抑制RNAPII转录，正反馈（而不是补偿）的指示。这种抑制需要主动的细胞质mRNA降解，这导致转录前起始复合物的组分向启动子DNA的募集受损。Importin α/β介导的核输入对于这种反馈信号传导至关重要，这表明在细胞质和细胞核之间移位的蛋白质将mRNA衰变与转录联系起来。我们还表明，由病毒核酸酶激活的类似途径同样依赖于核蛋白的输入。总的来说，这些数据表明，加速的mRNA衰变导致mRNA转录的抑制，从而放大了基因表达的关闭。这突出了细胞对威胁做出反应的保守基因调控机制。
RNA abundance is generally sensitive to perturbations in decay and synthesis rates, but crosstalk between RNA polymerase II transcription and cytoplasmic mRNA degradation often leads to compensatory changes in gene expression. Here, we reveal that widespread mRNA decay during early apoptosis represses RNAPII transcription, indicative of positive (rather than compensatory) feedback. This repression requires active cytoplasmic mRNA degradation, which leads to impaired recruitment of components of the transcription preinitiation complex to promoter DNA. Importin α/β-mediated nuclear import is critical for this feedback signaling, suggesting that proteins translocating between the cytoplasm and nucleus connect mRNA decay to transcription. We also show that an analogous pathway activated by viral nucleases similarly depends on nuclear protein import. Collectively, these data demonstrate that accelerated mRNA decay leads to the repression of mRNA transcription, thereby amplifying the shutdown of gene expression. This highlights a conserved gene regulatory mechanism by which cells respond to threats.
影响因子：
3.7
作者：
Düring L;Thorsen M;Petersen DS;Køster B;Jensen TH;Holmberg S
通讯作者：
Holmberg S