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PreprintCited by 5Genomics and Chromatin DynamicsRNA Research and SplicingNuclear Structure and Function

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

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Bhuiyan, Tanja, Mendoza Sanchez, Paulina K., Arecco, Niccolò, Kim, Juhyeong, Nizamuddin, Sheikh, Prunotto, Andrea, Tekman, Mehmet, Biniossek, Martin L., Koidl, Stefanie, Hugel, Thorsten, Arnold, Sebastian J.·2024·Cell Reports
DOI 10.1101/2024.02.05.578926

Preprint — published as 10.1016/j.celrep.2025.115616 · Paper page

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Abstract

Summary: 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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Metadata

Authors
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.
Affiliations
  • University of Freiburg (DE)
  • Centre for Genomic Regulation (ES)
Corresponding author
  • Bhuiyan, Tanja
  • Arnold, Sebastian J.
ORCID
Venue
Cell Reports
Publisher
openRxiv
Published
2024-02-05
Volume
44
Issue
5
Pages
115616-115616
ISSN
2211-1247 (ISSN-L)
DOI
10.1101/2024.02.05.578926
OpenAlex
W4409790373
Cited by
5
References
1
Citations by year
2026: 2 · 2025: 3
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
Funders
  • European Molecular Biology Organization (LTF 695-2019)
  • Deutsche Forschungsgemeinschaft (SFB 992, EXC‐2189, INST 39/1170-1 FUGG, 390939984, 992/1 2012, 192904750, AR 732/3–1, SFB 992/1, SFB 992/1 2012, CRC1381, 403222702, CRC992)
  • Bundesministerium für Bildung und Forschung (EXC-2189, 031A538A, 390939984)
  • Albert-Ludwigs-Universität Freiburg (EXC-2189, 390939984)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
TFIID, intrinsically disordered regions, nuclear speckles, condensate, RNA splicing, alternative splicing, SRRM2, TATA-binding protein, transcription initiation, RNA polymerase II, nuclear compartmentalization, protein-protein interaction
MeSH terms
RNA Splicing Factors, Cell Nucleus, HeLa Cells, Humans, Promoter Regions, Genetic, Protein Binding, RNA Splicing, Transcription Factor TFIID, TATA-Binding Protein Associated Factors

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