{
  "abstract": "Background: X-chromosome inactivation (XCI) evolved independently in eutherian and marsupial mammals, where it is orchestrated by the unrelated long non-coding RNAs Xist and RSX, respectively. Xist organizes a repressive nuclear compartment through multivalent RNA-protein interactions, but whether RSX exploits similar biophysical principles remains unknown. A recent paper has identified bona fide RSX interacting proteins. Results: We integrated proteome-scale RNA-protein interaction prediction, experimental validation, phase-separation propensity analysis, functional annotation and comparative RNA-structure modelling to characterize the RSX interaction landscape. Using catRAPID, we ranked 1,168 RNA-binding proteins from the native Monodelphis domestica proteome. Predictions were significantly enriched for experimentally identified RSX interactors, with 4.85-fold enrichment among the top 50 candidates (P approximately 1.6 x 10-5), increasing to approximately eightfold for proteins shared by the experimental RSX and Xist interactomes (P approximately 2 x 10-6). Among 30 high-confidence RSX interactors, 13 were experimentally supported, 17 were previously unrecognized candidates and 17 exhibited high phase-separation propensity. The network was enriched in ribonucleoprotein granules and nuclear bodies and converged on m6A regulators and SR-family splicing factors. Comparative modelling detected no conserved secondary or tertiary architecture between RSX and Xist. Conclusions: RSX and Xist appear to have converged not through RNA sequence or global structure, but through recruitment of related, condensation-prone protein networks. These findings identify interaction-network and biophysical convergence as a potential principle of lncRNA-mediated chromosome regulation and provide testable candidates for determining whether RSX establishes a condensate-like compartment on the marsupial inactive X.",
  "abstract_shown": true,
  "affiliations": [
    "Unit of Cell and Developmental Biology, Department of Biology, University of Pisa, Strada Statale dell Abetone Brennero 4, 56123, Pisa, Italy"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "A. K. Danga"
    },
    {
      "name": "C. Canale"
    },
    {
      "name": "R. D. Ponti"
    },
    {
      "name": "G. G. Tartaglia"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Cerase"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eehrr5zbsckg6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.18.752704",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752704v1.full",
  "id": "eehrr5zbsckg6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752704v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|RNA Research and Splicing"
    ]
  ],
  "openalex": "W7214187441",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752704v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eehrr5zbsckg6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:15Z",
      "native_id": "10.64898/2026.09.18.752704",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752704v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Phase Separation Potential of Marsupial RSX RNA Reveals Convergent Evolution of X-Chromosome Inactivation Mechanisms",
  "title_text": "Phase Separation Potential of Marsupial RSX RNA Reveals Convergent Evolution of X-Chromosome Inactivation Mechanisms",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:15Z",
  "url": "https://research.draconitic.com/paper/eehrr5zbsckg6",
  "venue": "bioRxiv",
  "versions": []
}