ArticleNature communications2026
AACRNL evolved from virulence factor to epigenetic parasite driving genome expansion in free-living eukaryotes.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.