{
  "id": 6290239,
  "title": "Cellular modifiers of TDP-43 phase transition and cytoplasmic aggregation",
  "url": "https://urgent.news/2026/09/08/cellular-modifiers-of-tdp-43-phase-transition-and-cytoplasmic",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-08T00:00:00.000Z",
  "source": {
    "name": "eLife",
    "slug": "elife",
    "url": "https://elifesciences.org/articles/110172"
  },
  "original_language": "en",
  "account": "TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein, can form liquid-like assemblies within the nucleus, which may affect its aggregation and neurotoxicity. However, the factors that control the transition of TDP-43 from a liquid to a solid phase are not well understood. In this study, researchers employed both chemical and genome-wide genetic screens to uncover cellular factors that influence the phase behavior of an RNA-binding-defective TDP-43 mutant.\n\nThe screens revealed several cellular processes that regulate TDP-43 phase behavior, including RNA splicing, protein translation, proteostasis imbalance, and nuclear export. To better understand these mechanisms, the researchers created a semi-permeabilized cell system that approximates the TDP-43 phase transition in a laboratory setting. They found that inhibiting nuclear export, the process by which proteins and RNA molecules move between the nucleus and the cytoplasm, alters the nuclear environment in a way that promotes the liquid-like phase of TDP-43 and reduces its aggregation.\n\nThe implications of these findings extend beyond the lab, as the researchers tested their approach in a brain organoid model carrying an ALS-associated mutation. In this model, inhibiting nuclear export reduced the accumulation of a toxic form of TDP-43 called phospho-TDP-43. This discovery offers new insights into the link between nuclear transport and TDP-43 phase dynamics, opening doors for further investigation into the underlying causes of ALS and potential therapeutic targets.",
  "summary": "RNA-binding protein TAR DNA-binding protein 43 (TDP-43) can form liquid-like nuclear assemblies whose phase behavior is thought to influence its aggregation propensity and neurotoxic activity. The mechanisms that govern the liquid-to-solid phase transition of TDP-43 remain poorly defined. Here, we combined chemical and genome-wide genetic screens to identify cellular factors that modulate the…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}