PDF(Pubmed)
Abstract：
RNA-directed transposon silencing operates in the mammalian soma and germline to safeguard genomic integrity. The piRNA pathway and the HUSH complex identify active transposons through recognition of their nascent transcripts, but mechanistic understanding of how these distinct pathways evolved is lacking. TASOR is an essential component of the HUSH complex. TASOR\'s DUF3715 domain adopts a pseudo-PARP structure and is required for transposon silencing in a manner independent of complex assembly. TEX15, an essential piRNA pathway factor, also contains the DUF3715 domain. Here, we show that TASOR\'s and TEX15\'s DUF3715 domain share extensive structural homology. We found that the DUF3715 domain arose in early eukaryotes and that in vertebrates it is restricted to TEX15, TASOR, and TASORB orthologs. While TASOR-like proteins are found throughout metazoa, TEX15 is vertebrate-specific. The branching of TEX15 and the TASOR-like DUF3715 domain likely occurred in early metazoan evolution. Remarkably, despite this vast evolutionary distance, the DUF3715 domain from divergent TEX15 sequences can functionally substitute the DUF3715 domain of TASOR and mediates transposon silencing. We have thus termed this domain of unknown function as the RNA-directed pseudo-PARP transposon silencing (RDTS) domain. In summary, we show an unexpected functional link between these critical transposon silencing pathways.
摘要：
RNA指导的转座子沉默在哺乳动物体细胞和种系中起作用以保护基因组完整性。piRNA通路和HUSH复合物通过识别其新生转录物识别活性转座子，但是缺乏对这些不同途径如何进化的机械理解。TASOR是HUSH复合物的重要组成部分。TSOR的DUF3715结构域采用伪PARP结构，并且是转座子沉默所必需的，其方式与复杂组装无关。TEX15，一种必需的piRNA途径因子，还包含DUF3715域。这里,我们显示TASOR和TEX15的DUF3715结构域具有广泛的结构同源性。我们发现DUF3715结构域出现在早期真核生物中，而在脊椎动物中它仅限于TEX15，TASOR，和TASORB直系同源物。虽然在后生动物中发现了TSOR样蛋白，TEX15是脊椎动物特异性的。TEX15和TSOR样DUF3715结构域的分支可能发生在早期后生动物进化中。值得注意的是,尽管进化距离很远,来自不同TEX15序列的DUF3715结构域可以在功能上替代TSOR中的相同结构域并介导转座子沉默。因此，我们将此功能未知的结构域称为RNA指导的假PARP转座子沉默（RDTS）结构域。总之,我们显示了这些关键转座子沉默途径之间意想不到的功能联系。
