TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing

Bhuiyan, T.; Mendoza Sanchez, P. K.; Arecco, N.; Kim, J.; Nizamuddin, S.; Prunotto, A.; Tekman, M.; Biniossek, M. L.; Koidl, S.; Hugel, T.; Arnold, S. J.

doi:10.1101/2024.02.05.578926

bioRxiv · 10.1101/2024.02.05.578926

TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing

Bhuiyan, T.·Mendoza Sanchez, P. K.·Arecco, N.·Kim, J.·Nizamuddin, S.·Prunotto, A.·Tekman, M.·Biniossek, M. L.·Koidl, S.·Hugel, T.·Arnold, S. J.

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Abstract

TFIID is an essential basal transcription factor, crucial for RNA polymerase II (pol II) promoter recognition and transcription initiation. The TFIID complex consists of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs) that contain intrinsically disordered regions (IDRs) with currently unknown functions. Here, we show that a conserved IDR drives TAF2 condensation in nuclear speckles, independently of other TFIID subunits. Quantitative mass spectrometry analyses reveal that the TAF2 IDR specifically interacts with the nuclear speckle and spliceosome-associated protein SRRM2. Consequently, TAF2 recruits SRRM2 to TFIID to form non-canonical TFIID-SRRM2 complexes. Reduced SRRM2 recruitment elicits alternative splicing events in RNAs coding for proteins involved in transcription and transmembrane transport. Further, genome-wide binding analyses suggest TAF2 shuttling between nuclear speckles and pol II promoters. This study identifies an IDR of the basal transcription machinery as a molecular guide for protein partitioning into nuclear compartments, controlling protein complex composition and pre-mRNA splicing.

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Bhuiyan, T., Mendoza Sanchez, P. K., Arecco, N., Kim, J., Nizamuddin, S., Prunotto, A., Tekman, M., Biniossek, M. L., Koidl, S., Hugel, T., Arnold, S. J.. 2024-02-05. TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing. https://doi.org/10.1101/2024.02.05.578926

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