DNA damage induces targeted, genome-wide variation of poly(A) sites in budding yeast.
DNA damage induces targeted, genome-wide variation of poly(A) sites in budding yeast.
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DOI：
10.1101/gr.144964.112
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发表时间：
2013-10
期刊：
影响因子：
7
通讯作者：
Moore CL
中科院分区：
文献类型：
--
作者：
Graber JH;Nazeer FI;Yeh PC;Kuehner JN;Borikar S;Hoskinson D;Moore CL
系统对DNA损伤和其他胁迫的反应是一个复杂的过程，包括几乎所有基因表达阶段的调节和活性的变化。真核生物使用的一种基因调控机制是在不同的转录物亚型中进行选择，这些转录物在多聚腺苷化[聚(A)]位点上存在差异，导致编码序列或控制翻译、稳定性和定位的3‘非编码区部分发生变化。为了确定这种调控手段在应对DNA损伤时的使用程度，我们对暴露于紫外线模拟物4-硝基喹啉1-氧化物(4NQO)后酿酒酵母中聚(A)位点的使用进行了全局分析。经4NQO处理后，有2,031个基因的Poly(A)位点分布发生显著变化，并倾向于丢失短转录本，其中许多基因的Poly(A)位点位于蛋白质编码序列(CDS)内。我们进一步探索了一种可能的机制，这种机制可能导致了mRNA异构体的广泛差异。Poly(A)位点谱的改变与细胞提取液中的切割和多聚腺苷酸化的抑制以及mRNA3‘端加工复合体中几个关键亚基的水平降低有关。序列分析确定了推测抑制和增强聚(A)位点侧翼的顺式作用元件的差异，暗示了一种可能区分可变和组成聚(A)位点的机制。我们的分析表明，mRNA长度的变化是DNA损伤调控反应的重要组成部分。
Systemic response to DNA damage and other stresses is a complex process that includes changes in the regulation and activity of nearly all stages of gene expression. One gene regulatory mechanism used by eukaryotes is selection among alternative transcript isoforms that differ in polyadenylation [poly(A)] sites, resulting in changes either to the coding sequence or to portions of the 3′ UTR that govern translation, stability, and localization. To determine the extent to which this means of regulation is used in response to DNA damage, we conducted a global analysis of poly(A) site usage in Saccharomyces cerevisiae after exposure to the UV mimetic, 4-nitroquinoline 1-oxide (4NQO). Two thousand thirty-one genes were found to have significant variation in poly(A) site distributions following 4NQO treatment, with a strong bias toward loss of short transcripts, including many with poly(A) sites located within the protein coding sequence (CDS). We further explored one possible mechanism that could contribute to the widespread differences in mRNA isoforms. The change in poly(A) site profile was associated with an inhibition of cleavage and polyadenylation in cell extract and a decrease in the levels of several key subunits in the mRNA 3′-end processing complex. Sequence analysis identified differences in the cis-acting elements that flank putatively suppressed and enhanced poly(A) sites, suggesting a mechanism that could discriminate between variable and constitutive poly(A) sites. Our analysis indicates that variation in mRNA length is an important part of the regulatory response to DNA damage.
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影响因子：
64.8
作者：
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