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| Main Authors: | , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Nature communications
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41605925/ |
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| _version_ | 1868266092674154498 |
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| author | Xu, Tianjun Geng, Shang Lv, Xing Xing, Qianru Sun, Yuena |
| author_facet | Xu, Tianjun Geng, Shang Lv, Xing Xing, Qianru Sun, Yuena Xu, Tianjun Geng, Shang Lv, Xing Xing, Qianru Sun, Yuena |
| collection | PubMed - marine biology |
| contents | AACRNL evolved from virulence factor to epigenetic parasite driving genome expansion in free-living eukaryotes. Xu, Tianjun Geng, Shang Lv, Xing Xing, Qianru Sun, Yuena Virulence Factors Epigenesis, Genetic ADP Ribose Transferases Animals Humans Evolution, Molecular Genome Eukaryota Crinkler effectors are iconic toxins deployed by pathogens to suppress host immunity, a function long thought exclusive to pathogenic species. Here, we uncover a striking evolutionary twist: an ADP-ribosyltransferase-associated Crinkler-like protein that has repurposed its toxin-derived activity to function as an epigenetic parasite in free-living eukaryotes, challenging the paradigm that Crinkler effectors are exclusively pathogen-restricted virulence factors. The ADP-ribosyltransferase-associated Crinkler-like protein retains a functional mono-ADP-ribosyltransferase domain homologous to diphtheria toxin, yet exhibits degeneration of N-terminal host-targeting domain, severing ties to canonical pathogenic functions. This activity enables dual subversion of host mechanisms: the ADP-ribosyltransferase-associated Crinkler-like protein mono-ADP-ribosylates the EZH2, reducing H3K27me3-mediated silencing and reactivating its own locus and adjacent transposons to drive replicative amplification; simultaneously, it modifies the immune adaptor TRAF6, suppressing NF-κB and IRF3 pathways to weaken innate immune surveillance and facilitate sustained propagation within the host genome. Notably, this parasitic strategy is countered by host detoxification: TRAF6 ubiquitinates ADP-ribosyltransferase-associated Crinkler-like protein, targeting it for proteasomal degradation. Together, our findings reveal how a toxin-derived effector escaped pathogenic contexts to evolve as a selfish genomic element, leveraging toxin-like activity to subvert epigenetic and immune barriers and redefining the evolutionary potential of Crinkler toxins as drivers of genomic conflict beyond pathogenicity. |
| format | Artículo científico |
| id | pubmed_41605925 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | AACRNL evolved from virulence factor to epigenetic parasite driving genome expansion in free-living eukaryotes. Xu, Tianjun Geng, Shang Lv, Xing Xing, Qianru Sun, Yuena Virulence Factors Epigenesis, Genetic ADP Ribose Transferases Animals Humans Evolution, Molecular Genome Eukaryota AACRNL evolved from virulence factor to epigenetic parasite driving genome expansion in free-living eukaryotes. Xu, Tianjun Geng, Shang Lv, Xing Xing, Qianru Sun, Yuena Virulence Factors Epigenesis, Genetic ADP Ribose Transferases Animals Humans Evolution, Molecular Genome Eukaryota Crinkler effectors are iconic toxins deployed by pathogens to suppress host immunity, a function long thought exclusive to pathogenic species. Here, we uncover a striking evolutionary twist: an ADP-ribosyltransferase-associated Crinkler-like protein that has repurposed its toxin-derived activity to function as an epigenetic parasite in free-living eukaryotes, challenging the paradigm that Crinkler effectors are exclusively pathogen-restricted virulence factors. The ADP-ribosyltransferase-associated Crinkler-like protein retains a functional mono-ADP-ribosyltransferase domain homologous to diphtheria toxin, yet exhibits degeneration of N-terminal host-targeting domain, severing ties to canonical pathogenic functions. This activity enables dual subversion of host mechanisms: the ADP-ribosyltransferase-associated Crinkler-like protein mono-ADP-ribosylates the EZH2, reducing H3K27me3-mediated silencing and reactivating its own locus and adjacent transposons to drive replicative amplification; simultaneously, it modifies the immune adaptor TRAF6, suppressing NF-κB and IRF3 pathways to weaken innate immune surveillance and facilitate sustained propagation within the host genome. Notably, this parasitic strategy is countered by host detoxification: TRAF6 ubiquitinates ADP-ribosyltransferase-associated Crinkler-like protein, targeting it for proteasomal degradation. Together, our findings reveal how a toxin-derived effector escaped pathogenic contexts to evolve as a selfish genomic element, leveraging toxin-like activity to subvert epigenetic and immune barriers and redefining the evolutionary potential of Crinkler toxins as drivers of genomic conflict beyond pathogenicity. |
| title | AACRNL evolved from virulence factor to epigenetic parasite driving genome expansion in free-living eukaryotes. |
| topic | Virulence Factors Epigenesis, Genetic ADP Ribose Transferases Animals Humans Evolution, Molecular Genome Eukaryota |
| url | https://pubmed.ncbi.nlm.nih.gov/41605925/ |