ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Preservation of ALYREF Phase Separation Mitigates Doxorubicin-Induced Cardiomyocyte DNA Damage and Cardiotoxicity.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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
2 citing papers in PubMed.
- 5-Methylcytidine RNA Epitranscriptomics in Women's Health and Disease: Mechanisms and Clinical Implications.Cells · 2026Review
- Preservation of ALYREF Phase Separation Mitigates Doxorubicin-Induced Cardiomyocyte DNA Damage and Cardiotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
The clinical utility of the anticancer agent doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. ALYREF, a nuclear protein that preserves genomic stability through interactions with intranuclear components or as an m⁵C-binding regulator of mRNA maturation and export, has not been previously implicated in DOX-induced cardiotoxicity (DIC). Here, the role and underlying mechanisms of ALYREF in the pathogenesis of DIC are investigated. The findings demonstrate that ALYREF expression is markedly reduced in a murine model of DIC. Myocardial-specific overexpression of ALYREF attenuates DOX-induced DNA damage and cardiomyocyte apoptosis, whereas cardiac-specific knockout of ALYREF (ALYREF CKO) exacerbates DOX-induced cardiac dysfunction. Mechanistically, it is identified that nuclear DOX directly binds to the aspartate residue (D171) within the intrinsically disordered regions (IDRs) of ALYREF, disrupting its liquid-liquid phase separation (LLPS) and promoting its ubiquitin-mediated degradation. The condensate state of ALYREF is essential for maintaining the integrity of the NORAD-activated ribonucleoprotein complex 1 (NARC1). Consequently, disruption of ALYREF LLPS leads to dissociation of the NARC1 complex, resulting in DNA damage and apoptosis in CMs. Collectively, these findings reveal a previously unrecognized mechanism by which DIC via interference with ALYREF condensates, offering new insight into the molecular basis of DIC.
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.