【原】TASOR是一种伪PARP，用于指导HUSH复合物组装和表观遗传转座子控制

 TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control

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|核心内容：

HUSH复合物抑制逆转录病毒、转座子和基因，以维持脊椎动物基因组的完整性。 

HUSH调节表观遗传标记H3K9me3的沉积，但它的三个核心亚基TASOR、MPP8和Periphilin如何促进复合物的组装和靶向性尚不清楚。 

在这里，我们定义了HUSH组装的生化基础，发现其模块化结构类似于酵母RNA诱导的转录沉默复合物。 

中央HUSH亚基TASOR与RNA加工成分有关。 

在转录基因中，H3K9me3在LINE-1重复序列和重复外显子上的沉积是必需的。 

在先前的研究背景下，这表明RNA中间体对HUSH活性很重要。 

我们解剖了转基因抑制所必需的TASOR和MPP8结构域。 

结构-功能分析表明，TASOR具有靶向H3K9me3沉积所必需的催化活性PARP结构域。 

我们的结论是TASOR是一种多功能伪PARP，它指导重复基因组靶点的HUSH组装和表观遗传调控。

 Schematic model of HUSH repression

原文摘要：

The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits — TASOR, MPP8 and Periphilin — contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture resembles the yeast RNA-induced transcriptional silencing complex. TASOR, the central HUSH subunit, associates with RNA processing components. TASOR is required for H3K9me3 deposition over LINE-1 repeats and repetitive exons in transcribed genes. In the context of previous studies, this suggests that an RNA intermediate is important for HUSH activity. We dissect the TASOR and MPP8 domains necessary for transgene repression. Structure-function analyses reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition. We conclude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulation of repetitive genomic targets.

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参考文献：https:///10.1038/s41467-020-18761-6

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