The DUF3715 domain has a conserved role in RNA-directed transposon silencing

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 orthologues. While TASOR-like proteins are found throughout metazoa, TEX15 is vertebrate specific. The branching of TEX15 and 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 for the same domain in 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.

Prigozhin, Daniil MLawrence Berkeley National Laboratory (author)
Douse, ChristopherLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Epigenetik och kromatindynamik,Forskargrupper vid Lunds universitet,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Epigenetics and Chromatin Dynamics,Lund University Research Groups(Swepub:lu)ch2676do (author)
Kaji, KeisukeUniversity of Edinburgh (author)
Cook, Atlanta GUniversity of Edinburgh (author)
O'Carroll, DonalUniversity of Edinburgh (author)
University of EdinburghLawrence Berkeley National Laboratory (creator_code:org_t)

By the author/editor: Schöpp, Theresa; Prigozhin, Danii ...; Douse, Christoph ...; Kaji, Keisuke; Cook, Atlanta G; O'Carroll, Donal

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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