Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1
Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1
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DOI：
10.1038/nsmb972
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发表时间：
2005-09-01
影响因子：
16.8
通讯作者：
Marzluff, WF
中科院分区：
文献类型：
--
作者：
Kaygun, H;Marzluff, WF
真核细胞协调调节组蛋白和DNA的合成。在哺乳动物细胞中，组蛋白合成的大部分调控发生在转录后，通过调节组蛋白mRNA的浓度。随着细胞进入S期，组蛋白mRNA水平升高，并在S期结束时迅速降解。此外，抑制DNA合成会导致组蛋白mrna的快速降解。复制依赖性组蛋白mrna是唯一不被聚腺苷化的后生动物mrna。相反，它们以保守的茎环结构结束，这是组蛋白mRNA半衰期与DNA合成耦合调节所需的唯一顺式作用元件。在这里，我们发现组蛋白mrna的调节降解需要Upf1（无义介导的衰变途径的关键调节剂）和ATR （DNA损伤检查点途径的关键调节剂）在复制应激过程中被激活。
Eukaryotic cells coordinately regulate histone and DNA synthesis. In mammalian cells, most of the regulation of histone synthesis occurs post-transcriptionally by regulating the concentrations of histone mRNA. As cells enter S phase, histone mRNA levels increase, and at the end of S phase they are rapidly degraded. Moreover, inhibition of DNA synthesis causes rapid degradation of histone mRNAs. Replication-dependent histone mRNAs are the only metazoan mRNAs that are not polyadenylated. Instead, they end with a conserved stem-loop structure, which is the only cis-acting element required for coupling regulation of histone mRNA half-life with DNA synthesis. Here we show that regulated degradation of histone mRNAs requires Upf1, a key regulator of the nonsense-mediated decay pathway, and ATR, a key regulator of the DNA damage checkpoint pathway activated during replication stress.