A combinatorial pre-mRNP retention factor network couples nuclear speckle architecture to splicing quality control
- 1Biozentrum, University of Basel, Basel, Switzerland.
Abstract
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.
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BibTeX
@misc{doerner2026combinatorial,
title = {{A combinatorial pre-mRNP retention factor network couples nuclear speckle architecture to splicing quality control}},
author = {K. Doerner and K. Kurth and N. Beuret and N. Beer and M. K. Jones and K. Davey and L. Stadelmann and D. Huegli and A. Ferrand and G. Basile and S. Luescher and J. Ule and F. Voigt and M. Hondele},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.754972},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.754972v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A combinatorial pre-mRNP retention factor network couples nuclear speckle architecture to splicing quality control
AU - K. Doerner
AU - K. Kurth
AU - N. Beuret
AU - N. Beer
AU - M. K. Jones
AU - K. Davey
AU - L. Stadelmann
AU - D. Huegli
AU - A. Ferrand
AU - G. Basile
AU - S. Luescher
AU - J. Ule
AU - F. Voigt
AU - M. Hondele
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.754972
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.754972v1
AB - 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.
ER -