A combinatorial pre-mRNP retention factor network couples nuclear speckle architecture to splicing quality control
Year: 2026
Type: preprint
Abstract: Summary Cells must prevent incompletely spliced transcripts from entering the cytoplasm, yet how splicing status is recognized and converted into selective nuclear retention remains unclear. Here, we identify a network of RNA-binding proteins that retain pre-mRNPs within nuclear speckles. Proteomic analysis of splicing intermediates accumulated in nuclear speckles identified a set of retention factors including BCLAF1, THRAP3 and SRSF7 that anchor pre-mRNPs to the SON scaffold and are required for pre-mRNP retention in speckles. Distinct RNA-binding patterns and transcript-specific retention factor requirements suggest that multiple mRNP features tune retention combinatorially. Super-resolution imaging revealed that the SON and SRRM2 speckle scaffolds form interdigitated networks with RNA enriched along networks and within interstitial speckle lumens. This architecture remodels in response to pre-mRNP load and is disrupted upon depletion of retention factors. Together, these findings define a pre-mRNP quality-control pathway that links splicing state to nuclear retention and the dynamic organization of nuclear speckles.
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7214759770