TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors
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)...
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| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003870 |
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| author | Tanja Bhuiyan Niccolò Arecco Paulina Karen Mendoza Sanchez Juhyeong Kim Carsten Schwan Sophie Weyrauch Sheikh Nizamuddin Andrea Prunotto Mehmet Tekman Martin L. Biniossek Bettina Knapp Stefanie Koidl Friedel Drepper Pitter F. Huesgen Robert Grosse Thorsten Hugel Sebastian J. Arnold |
| author_facet | Tanja Bhuiyan Niccolò Arecco Paulina Karen Mendoza Sanchez Juhyeong Kim Carsten Schwan Sophie Weyrauch Sheikh Nizamuddin Andrea Prunotto Mehmet Tekman Martin L. Biniossek Bettina Knapp Stefanie Koidl Friedel Drepper Pitter F. Huesgen Robert Grosse Thorsten Hugel Sebastian J. Arnold |
| author_sort | Tanja Bhuiyan |
| collection | DOAJ |
| description | 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 to nuclear speckle condensates independently of other TFIID subunits. Quantitative mass spectrometry analyses reveal TAF2 proximity to RNA splicing factors including specific interactions of the TAF2 IDR with SRRM2 in nuclear speckles. Deleting the IDR from TAF2 does not majorly impact global gene expression but results in changes of alternative splicing events. Further, genome-wide binding analyses suggest that the TAF2 IDR impedes TAF2 promoter association by guiding TAF2 to nuclear speckles. This study demonstrates that an IDR within the large multiprotein complex TFIID controls nuclear compartmentalization and thus links distinct molecular processes, namely transcription initiation and RNA splicing. |
| format | Article |
| id | doaj-art-d3d9a23049b1459d9be85c692a4c3ff7 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-d3d9a23049b1459d9be85c692a4c3ff72025-08-20T03:14:02ZengElsevierCell Reports2211-12472025-05-0144511561610.1016/j.celrep.2025.115616TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factorsTanja Bhuiyan0Niccolò Arecco1Paulina Karen Mendoza Sanchez2Juhyeong Kim3Carsten Schwan4Sophie Weyrauch5Sheikh Nizamuddin6Andrea Prunotto7Mehmet Tekman8Martin L. Biniossek9Bettina Knapp10Stefanie Koidl11Friedel Drepper12Pitter F. Huesgen13Robert Grosse14Thorsten Hugel15Sebastian J. Arnold16Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany; Department of Urology, Medical Center–University of Freiburg, Faculty of Medicine, Breisacher Strasse 66, 79106 Freiburg, Germany; Corresponding authorGenome Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, SpainDepartment of Urology, Medical Center–University of Freiburg, Faculty of Medicine, Breisacher Strasse 66, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, 79106 Freiburg, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, GermanyInstitute of Physical Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstrasse 25, 79104 Freiburg, GermanyInstitute of Physical Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Alberstrasse 19A, 79104 Freiburg, GermanyDepartment of Urology, Medical Center–University of Freiburg, Faculty of Medicine, Breisacher Strasse 66, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, 79106 Freiburg, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, GermanyDatenintegrationszentrum, Medical Center–University of Freiburg, Faculty of Medicine, Georges-Köhler-Allee 302, 79110 Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstrasse 25, 79104 Freiburg, GermanyInstitute of Molecular Medicine and Cell Research, University of Freiburg, Stefan-Meier-Strasse 17, 79104 Freiburg, GermanyInstitute for Biology II, University of Freiburg, Schänzlestrasse 1, 79104 Freiburg, GermanyDepartment of Urology, Medical Center–University of Freiburg, Faculty of Medicine, Breisacher Strasse 66, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, 79106 Freiburg, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, GermanyInstitute for Biology II, University of Freiburg, Schänzlestrasse 1, 79104 Freiburg, GermanyInstitute for Biology II, University of Freiburg, Schänzlestrasse 1, 79104 Freiburg, Germany; BIOSS and CIBSS Signalling Research Centres, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany; BIOSS and CIBSS Signalling Research Centres, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, GermanyInstitute of Physical Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany; BIOSS and CIBSS Signalling Research Centres, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany; BIOSS and CIBSS Signalling Research Centres, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, Germany; Corresponding authorSummary: 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 to nuclear speckle condensates independently of other TFIID subunits. Quantitative mass spectrometry analyses reveal TAF2 proximity to RNA splicing factors including specific interactions of the TAF2 IDR with SRRM2 in nuclear speckles. Deleting the IDR from TAF2 does not majorly impact global gene expression but results in changes of alternative splicing events. Further, genome-wide binding analyses suggest that the TAF2 IDR impedes TAF2 promoter association by guiding TAF2 to nuclear speckles. This study demonstrates that an IDR within the large multiprotein complex TFIID controls nuclear compartmentalization and thus links distinct molecular processes, namely transcription initiation and RNA splicing.http://www.sciencedirect.com/science/article/pii/S2211124725003870CP: Molecular biology |
| spellingShingle | Tanja Bhuiyan Niccolò Arecco Paulina Karen Mendoza Sanchez Juhyeong Kim Carsten Schwan Sophie Weyrauch Sheikh Nizamuddin Andrea Prunotto Mehmet Tekman Martin L. Biniossek Bettina Knapp Stefanie Koidl Friedel Drepper Pitter F. Huesgen Robert Grosse Thorsten Hugel Sebastian J. Arnold TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors Cell Reports CP: Molecular biology |
| title | TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors |
| title_full | TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors |
| title_fullStr | TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors |
| title_full_unstemmed | TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors |
| title_short | TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors |
| title_sort | taf2 condensation in nuclear speckles links basal transcription factor tfiid to rna splicing factors |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003870 |
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