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

Schöpp, Theresa ; Prigozhin, Daniil M ; Douse, Christopher LU ; Kaji, Keisuke ; Cook, Atlanta G and O'Carroll, Donal (2023) In RNA 29(10). p.1471-1480
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
RNA
volume
29
issue
10
pages
1471 - 1480
publisher
Cold Spring Harbor Laboratory Press (CSHL)
external identifiers
  • scopus:85171807180
  • pmid:37433650
ISSN
1355-8382
DOI
10.1261/rna.079693.123
language
English
LU publication?
yes
id
66f73f04-3d1a-4bee-bfcf-8b4b0bb94195
date added to LUP
2023-07-18 11:47:04
date last changed
2024-04-29 19:28:16
@article{66f73f04-3d1a-4bee-bfcf-8b4b0bb94195,
  abstract     = {{<p>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.</p>}},
  author       = {{Schöpp, Theresa and Prigozhin, Daniil M and Douse, Christopher and Kaji, Keisuke and Cook, Atlanta G and O'Carroll, Donal}},
  issn         = {{1355-8382}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{10}},
  pages        = {{1471--1480}},
  publisher    = {{Cold Spring Harbor Laboratory Press (CSHL)}},
  series       = {{RNA}},
  title        = {{The DUF3715 domain has a conserved role in RNA-directed transposon silencing}},
  url          = {{http://dx.doi.org/10.1261/rna.079693.123}},
  doi          = {{10.1261/rna.079693.123}},
  volume       = {{29}},
  year         = {{2023}},
}