{
  "id": 18027154,
  "title": "KH1 Domain of Poly C Binding Protein 1 (PCBP1) Interacts with Utrophin-A mRNA and Modulates Utrophin-A Expression in Mouse Myoblasts",
  "url": "https://urgent.news/2026/11/03/kh1-domain-of-poly-c-binding-protein-1-pcbp1-interacts-with-utrophin",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763282v1?rss=1"
  },
  "original_language": "en",
  "account": "Utrophin upregulation has the potential to improve Duchenne Muscular Dystrophy (DMD). In this study, researchers examined if murine poly(C)-binding protein 1 (PCBP1) interacts directly with utrophin-A mRNA and how this interaction influences utrophin-A expression in muscle cells. Due to the lack of an experimentally validated structure for murine PCBP1, AlphaFold2 was used to predict the structure of the full-length protein and its KH1-KH2 domain. The more reliable model of the KH1-KH2 domain was docked with the 5 UTR of the utrophin-A mRNA, and molecular dynamics simulations were performed to identify key hydrogen bond-forming residues in PCBP1. Isothermal titration calorimetry (ITC) revealed a thermodynamically favorable interaction between full-length PCBP1 and the 5 UTR of utrophin-A mRNA. However, a deletion mutant of PCBP1 lacking the predicted contact region did not show any interaction, which was also confirmed by an RNA immunoprecipitation assay in C2C12 cells. Contrary to this, PCBP1 overexpression in these cells resulted in decreased utrophin-A expression, while shRNA knockdown led to increased utrophin-A expression. A 5 UTR-luciferase reporter further supported these findings. Subcellular fractionation demonstrated that PCBP1 promotes the nuclear retention of utrophin-A transcripts and reduces their availability in the cytoplasm, with reciprocal effects upon PCBP1 knockdown. Based on previous research on PCBP2, these results suggest that both PCBP paralogs recognize the same 5 UTR element, and the KH1-dependent interaction represses utrophin-A by linking nuclear retention to reduced protein output. Thus, the PCBP1-5 UTR interaction is identified as a promising target for utrophin de-repression in DMD.",
  "summary": "Utrophin upregulation is an attractive strategy to ameliorate Duchenne Muscular Dystrophy (DMD). Here, we investigated whether the murine poly(C)-binding protein 1 (PCBP1) directly interacts with the utrophin-A mRNA, and how the interaction shapes the fate of utrophin-A in muscle cells. As no experimentally validated structure of the murine PCBP1 is available, AlphaFold2 was utilized to predict…",
  "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."
}