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U2AF2 controls alternative splicing in speckle-proximal regions in an RS domain-dependent manner - PubMed

5 hours ago
  • #alternative splicing
  • #U2AF2
  • #nuclear speckles
  • U2AF2 is crucial for 3' splice site recognition during spliceosome assembly.
  • Proximity labeling reveals U2AF2's functional partners in splicing, chromatin modification, transcription, 3' end processing, and RNA methylation.
  • Removal of the U2AF2 RS domain alters interactions, reduces nuclear speckle localization, and affects splicing genome-wide.
  • Cassette exons flanked by short introns near speckles are most impacted by U2AF2 knockdown or RS domain removal.
  • Phosphorylation sites in the U2AF2 RS domain are essential for normal splicing, indicating regulatory roles.
  • Alternatively spliced transcripts accumulate near speckles, with U2AF2 enrichment but limited local concentration.
  • Global U2AF2 reduction disproportionately affects splicing near nuclear speckles, highlighting spatial protein availability's role in splicing regulation.