The SR Protein B52/SRp55 Is Required for DNA Topoisomerase I Recruitment to Chromatin, mRNA Release and Transcription Shutdown
The SR Protein B52/SRp55 Is Required for DNA Topoisomerase I Recruitment to Chromatin, mRNA Release and Transcription Shutdown
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DOI：
10.1371/journal.pgen.1001124
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发表时间：
2010-09-01
期刊：
影响因子：
4.5
通讯作者：
Tazi, Jamal
中科院分区：
文献类型：
--
作者：
Juge, Francois;Fernando, Celine;Tazi, Jamal
DNA和RNA加工途径在真核细胞核中整合并相互连接，以允许有效的基因表达并维持基因组稳定性。DNA拓扑异构酶I（Topo I）是一种控制DNA超螺旋并作为SR蛋白家族剪接因子的特异性激酶的酶，其向高度转录的基因座的募集代表了一种机制，通过该机制可以协调转录和加工并避免基因组不稳定性。在这里，我们表明果蝇Topo I与SR蛋白B52结合并磷酸化。令人惊讶的是，在转基因果蝇中B52的高亲和力结合位点的表达不仅限制了B52的定位，而且限制了Topo I到这个单一转录位点的定位，而B52 RNAi敲低诱导了Topo I在核仁中的错误定位。受损的交付拓扑异构酶I热休克基因造成保留的mRNA在其网站的转录和延迟基因失活后热休克。我们的数据表明，B52提供拓扑I RNA聚合酶II活性染色质位点，并提供了第一个证据，DNA拓扑结构和mRNA的释放可以协调控制基因表达。
DNA- and RNA-processing pathways are integrated and interconnected in the eukaryotic nucleus to allow efficient gene expression and to maintain genomic stability. The recruitment of DNA Topoisomerase I (Topo I), an enzyme controlling DNA supercoiling and acting as a specific kinase for the SR-protein family of splicing factors, to highly transcribed loci represents a mechanism by which transcription and processing can be coordinated and genomic instability avoided. Here we show that Drosophila Topo I associates with and phosphorylates the SR protein B52. Surprisingly, expression of a high-affinity binding site for B52 in transgenic flies restricted localization, not only of B52, but also of Topo I to this single transcription site, whereas B52 RNAi knockdown induced mis-localization of Topo I in the nucleolus. Impaired delivery of Topo I to a heat shock gene caused retention of the mRNA at its site of transcription and delayed gene deactivation after heat shock. Our data show that B52 delivers Topo I to RNA polymerase II-active chromatin loci and provide the first evidence that DNA topology and mRNA release can be coordinated to control gene expression.