Nuclear deadenylation/polyadenylation factors regulate 3′ processing in response to DNA damage
Nuclear deadenylation/polyadenylation factors regulate 3′ processing in response to DNA damage
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DOI：
10.1038/emboj.2010.59
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发表时间：
2010-05-19
期刊：
影响因子：
11.4
通讯作者：
Kleiman, Frida E.
中科院分区：
文献类型：
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作者：
Cevher, Murat A.;Zhang, Xiaokan;Kleiman, Frida E.
我们先前表明，在DNA损伤条件下，细胞提取物中的mRNA 3'末端切割反应被强烈但短暂地抑制。裂解刺激因子-50（CstF-50）在这种反应中起作用，提供了转录偶联RNA加工和DNA修复之间的联系。在这项研究中，我们表明，CstF-50相互作用与核聚（A）特异性核糖核酸酶（PARN）使用在体外和紫外线暴露的细胞提取物。CstF-50/PARN复合物的形成在DNA损伤时抑制3'切割和激活去腺苷化中起作用。扩展这些结果，我们发现，肿瘤抑制因子BARD 1，这是在3'切割的UV诱导的抑制，强烈激活由PARN在CstF-50的存在下去腺苷化，CstF-50/BARD 1可以恢复帽结合蛋白-80（CBP 80）介导的PARN活性的抑制。我们还提供了证据表明，PARN沿着与CstF/BARD 1复合物参与调节内源性转录下的DNA损伤条件。我们推测，多聚腺苷酸化，deadenylation和肿瘤抑制因子之间的相互作用可能会阻止过早终止的信使的表达，有助于在不同的细胞条件下控制基因表达。The EMBO Journal（2010）29，1674-1687. doi：10.1038/doj.2010.59; 2010年4月8日在线发布
We previously showed that mRNA 3' end cleavage reaction in cell extracts is strongly but transiently inhibited under DNA-damaging conditions. The cleavage stimulation factor-50 (CstF-50) has a role in this response, providing a link between transcription-coupled RNA processing and DNA repair. In this study, we show that CstF-50 interacts with nuclear poly(A)-specific ribonuclease (PARN) using in vitro and in extracts of UV-exposed cells. The CstF-50/PARN complex formation has a role in the inhibition of 3' cleavage and activation of deadenylation upon DNA damage. Extending these results, we found that the tumour suppressor BARD1, which is involved in the UV-induced inhibition of 3' cleavage, strongly activates deadenylation by PARN in the presence of CstF-50, and that CstF-50/BARD1 can revert the cap-binding protein-80 (CBP80)mediated inhibition of PARN activity. We also provide evidence that PARN along with the CstF/BARD1 complex participates in the regulation of endogenous transcripts under DNA-damaging conditions. We speculate that the interplay between polyadenylation, deadenylation and tumour-suppressor factors might prevent the expression of prematurely terminated messengers, contributing to control of gene expression under different cellular conditions. The EMBO Journal (2010) 29, 1674-1687. doi: 10.1038/emboj.2010.59; Published online 8 April 2010