{
  "id": 18185298,
  "title": "RBM25 selectively stabilizes XBP1s mRNA independently of splicing factor activity",
  "url": "https://urgent.news/2026/11/04/rbm25-selectively-stabilizes-xbp1s-mrna-independently-of-splicing",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-04T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764219v1?rss=1"
  },
  "original_language": "en",
  "account": "A recently discovered protein, RBM25, plays a crucial role in stabilizing XBP1s mRNA independently of its splicing factor activity. This finding sheds light on a new regulatory checkpoint within the unfolded protein response (UPR), which is vital for maintaining endoplasmic reticulum (ER) proteostasis and preventing cell death during stress. The IRE1-XBP1 signaling axis, a key component of the UPR, generates the active transcription factor XBP1s through unconventional splicing of XBP1 mRNA. While the mechanisms behind IRE1 activation and XBP1 splicing have been well-studied, the post-transcriptional processes that maintain XBP1s expression are not fully understood. In this study, researchers identified RBM25 as a critical post-transcriptional regulator of the UPR that specifically stabilizes spliced XBP1 mRNA during ER stress. RBM25 binds to the 3' untranslated region of XBP1s mRNA, extending its half-life without influencing unspliced XBP1u transcripts or IRE1-mediated regulated decay (RIDD) targets. The depletion of RBM25 leads to reduced XBP1 transcriptional output, impaired adaptive UPR signaling, and increased sensitivity to ER stress-induced cell death across various stress conditions. These results reveal a previously unknown RNA-based regulatory mechanism that amplifies and sustains XBP1 signaling, ultimately fine-tuning the magnitude of the adaptive UPR and cellular survival in response to proteotoxic stress.",
  "summary": "The unfolded protein response (UPR) preserves endoplasmic reticulum (ER) proteostasis through coordinated transcriptional and translational programs that promote adaptation and prevents apoptosis. A central component of this response is the IRE1-XBP1 signaling axis, in which IRE1-mediated unconventional splicing of XBP1 mRNA generates the active transcription factor XBP1s. While the mechanisms…",
  "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."
}