{
  "id": 6547185,
  "title": "Widespread exon definition is promoted by the U1 snRNP 70K subunit and requires sites of contact with RNA Polymerase II",
  "url": "https://urgent.news/2026/09/09/widespread-exon-definition-is-promoted-by-the-u1-snrnp-70k-subunit",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-09T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749963v1?rss=1"
  },
  "original_language": "en",
  "account": "Recent research elucidates a key mechanism in pre-mRNA splicing, revealing that a subunit of U1 snRNP plays a pivotal role in the process. Scientists delved into this phenomenon by depleting the U1-70K subunit, which interacts with RNA polymerase II (RNAPII) during transcription. The findings indicate that this depletion leads to extensive exon skipping, suggesting a widespread method of exon definition.\n\nContrary to expectations, the exons with the most robust splice sites (SSs) are the ones most likely to be skipped. Moreover, modifying non-canonical SSs or using a drug that promotes similar SSs resulted in exon skipping when U1-70K was missing. This discovery points to a previously unrecognized function of U1-70K: destabilizing the interaction between U1 and the 5 SS, paving the way for the transition to the U6-5 SS necessary for efficient splicing following exon definition.\n\nFurther support for this theory came from observing that knocking down Prp28/DDX23, which facilitates U1-U6 exchange at the 5 SS, also induces exon skipping, mirroring the effects of U1-70K depletion. Additionally, swapping functional U1-70K with a mutant lacking the RNAPII interface in cells with degraded U1-70K induced widespread exon skipping. The authors propose that this process unfolds at the transcription elongation complex and is facilitated by the contact between U1-70K and RNAPII.",
  "summary": "Much pre-mRNA splicing initiates co-transcriptionally, but its mechanism is unclear. We investigated this process by degron depletion of the U1-70K subunit of U1 snRNP that contacts transcribing RNA polymerase II (RNAPII). U1-70K deficiency caused extensive exon skipping consistent with widespread exon definition. Surprisingly, exons with the strongest 5' splice sites (SSs) are skipped.…",
  "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."
}