热休克(HS)反应涉及HS基因的快速诱导,而转录抑制在大多数其他基因中建立得更慢。以前的数据表明,这种抑制是由抑制RNA聚合酶II(RNAPII)暂停释放引起的,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,而伸长率在HS时增加,加工能力显著下降,因此RNAPII经常无法到达基因的末端。的确,HS导致广泛的转录本在隐秘时提前终止,基因5'末端附近的内含子多腺苷酸化(IPA)位点,可能是通过抑制U1的电话脚本。这导致人类转录组的戏剧性重新配置,产生新的,以前没有注释,在细胞核中积累的短mRNA。一起,这些结果为高温下生长诱导的基本转录机制提供了新的思路,并表明在生理条件下可以发生全基因组向IPA位点使用的转变。
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.