Genome-wide mRNA surveillance is coupled to mRNA export
Genome-wide mRNA surveillance is coupled to mRNA export
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DOI：
10.1101/gad.1241204
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发表时间：
2004-11-01
影响因子：
10.5
通讯作者：
Silver, PA
中科院分区：
文献类型：
--
作者：
Hieronymus, H;Yu, MC;Silver, PA
mRNA的核输出是基因表达的中心步骤，其显示与转录和转录物加工的广泛偶联。然而，人们对mRNA的命运及其在破坏DNA模板和RNA本身的条件下的输出知之甚少。在这里，我们报告发现四个新的因素所需的mRNA出口，通过筛选所有注释的非必需的酿酒酵母基因。这些因子中的两个，mRNA监视因子Rrp6和DNA修复蛋白Lrp1，是彼此物理相互作用的核外泌体组分。我们发现，Lrp1介导特定的mRNA降解DNA损伤紫外线照射以及一般的mRNA降解。Lrp1需要Rrp6用于基因组定位到编码其mRNA靶的基因，而Rrp6基因组定位又与转录相关。此外，Rrp6和Lrp1都是修复UV诱导的DNA损伤所必需的。这些结果表明耦合的mRNA监视mRNA的出口，并建议特异性的RNA监视机制不同的转录本群体。从广义上讲，这些发现将DNA和RNA监视与mRNA输出联系起来。
Nuclear export of mRNA is a central step in gene expression that shows extensive coupling to transcription and transcript processing. However, little is known about the fate of mRNA and its export under conditions that damage the DNA template and RNA itself. Here we report the discovery of four new factors required for mRNA export through a screen of all annotated nonessential Saccharomyces cerevisiae genes. Two of these factors, mRNA surveillance factor Rrp6 and DNA repair protein Lrp1, are nuclear exosome components that physically interact with one another. We find that Lrp1 mediates specific mRNA degradation upon DNA-damaging UV irradiation as well as general mRNA degradation. Lrp1 requires Rrp6 for genomic localization to genes encoding its mRNA targets, and Rrp6 genomic localization in turn correlates with transcription. Further, Rrp6 and Lrp1 are both required for repair of UV-induced DNA damage. These results demonstrate coupling of mRNA surveillance to mRNA export and suggest specificity of the RNA surveillance machinery for different transcript populations. Broadly, these findings link DNA and RNA surveillance to mRNA export.