Heat shock induces premature transcript termination and reconfigures the human transcriptome.
Heat shock induces premature transcript termination and reconfigures the human transcriptome.
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DOI：
10.1016/j.molcel.2022.01.007
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发表时间：
2022-04-21
期刊：
影响因子：
16
通讯作者：
Svejstrup, Jesper Q.
中科院分区：
文献类型：
--
作者：
Cugusi, Simona;Mitter, Richard;Kelly, Gavin P.;Walker, Jane;Han, Zhong;Pisano, Paola;Wierer, Michael;Stewart, Aengus;Svejstrup, Jesper Q.
热休克(HS)反应涉及HS基因的快速诱导，而大多数其他基因的转录抑制建立得较慢。以前的数据表明，这种抑制是由于抑制RNA聚合酶II(RNAPII)的暂停释放造成的，但在这里，我们表明HS强烈影响转录周期的其他阶段。有趣的是，虽然伸长率在HS时增加，但加工性显著降低，因此RNAPII经常无法到达基因的末端。事实上，HS导致基因5‘端附近隐蔽的内含子多聚腺苷酸化(IPA)位点广泛的转录提前终止，可能是通过抑制U1端转录。这导致了人类转录组的戏剧性重组，产生了新的、以前没有注释的短mRNAs，这些mRNAs积累在细胞核中。总之，这些结果揭示了高温生长诱导的基本转录机制，并表明在生理条件下可以发生全基因组向使用IPA位点的转变。HS过程中转录下调是由过早终止引起的，HS过程中转录延伸率显著增加，HS扰乱远端转录并激活内含子HS中隐藏的PolyA位点，导致新的短mRNAs物种Cugusi等人的广泛合成。结果表明，在热休克过程中，伸长率显著增加，而在这些条件下观察到的转录全局下调是由于内含子中隐蔽的PA提前终止，导致大量新的短mRNA物种的合成。
The heat shock (HS) response involves rapid induction of HS genes, whereas transcriptional repression is established more slowly at most other genes. Previous data suggested that such repression results from inhibition of RNA polymerase II (RNAPII) pause release, but here, we show that HS strongly affects other phases of the transcription cycle. Intriguingly, while elongation rates increase upon HS, processivity markedly decreases, so that RNAPII frequently fails to reach the end of genes. Indeed, HS results in widespread premature transcript termination at cryptic, intronic polyadenylation (IPA) sites near gene 5′-ends, likely via inhibition of U1 telescripting. This results in dramatic reconfiguration of the human transcriptome with production of new, previously unannotated, short mRNAs that accumulate in the nucleus. Together, these results shed new light on the basic transcription mechanisms induced by growth at elevated temperature and show that a genome-wide shift toward usage of IPA sites can occur under physiological conditions. Transcription downregulation during HS is caused by premature termination Transcription elongation rate increases markedly during HS HS disrupts telescripting and activates cryptic poly(A) sites in introns HS results in widespread synthesis of new, short mRNAs species Cugusi et al. show that the elongation rate is dramatically increased during heat shock, while the global downregulation of transcription observed under these conditions is caused by premature termination at cryptic PAS in introns, which results in the synthesis of a large number of new, short mRNA species.
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影响因子：
7.7
作者：
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通讯作者：
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DOI：
10.1038/nrm.2017.73
发表时间：
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期刊：
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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