THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate
Summary: THOC5, a member of the THO complex, is essential for the 3′processing of some inducible genes, the export of a subset of mRNAs and stem cell survival. Here we show that THOC5 depletion results in altered 3′cleavage of >50% of mRNAs and changes in RNA polymerase II binding across genes. T...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222020570 |
| _version_ | 1797946195750944768 |
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| author | Mareike Polenkowski Aldrige Bernardus Allister Sebastian Burbano de Lara Andrew Pierce Bethany Geary Omar El Bounkari Lutz Wiehlmann Andrea Hoffmann Anthony D. Whetton Teruko Tamura Doan Duy Hai Tran |
| author_facet | Mareike Polenkowski Aldrige Bernardus Allister Sebastian Burbano de Lara Andrew Pierce Bethany Geary Omar El Bounkari Lutz Wiehlmann Andrea Hoffmann Anthony D. Whetton Teruko Tamura Doan Duy Hai Tran |
| author_sort | Mareike Polenkowski |
| collection | DOAJ |
| description | Summary: THOC5, a member of the THO complex, is essential for the 3′processing of some inducible genes, the export of a subset of mRNAs and stem cell survival. Here we show that THOC5 depletion results in altered 3′cleavage of >50% of mRNAs and changes in RNA polymerase II binding across genes. THOC5 is recruited close to high-density polymerase II sites, suggesting that THOC5 is involved in transcriptional elongation. Indeed, measurement of elongation rates in vivo demonstrated decreased rates in THOC5-depleted cells. Furthermore, THOC5 is preferentially recruited to its target genes in slow polymerase II cells compared with fast polymerase II cells. Importantly chromatin-associated THOC5 interacts with CDK12 (a modulator of transcription elongation) and RNA helicases DDX5, DDX17, and THOC6 only in slow polymerase II cells. The CDK12/THOC5 interaction promotes CDK12 recruitment to R-loops in a THOC6-dependent manner. These data demonstrate a novel function of THOC5 in transcription elongation. |
| first_indexed | 2024-04-10T21:07:02Z |
| format | Article |
| id | doaj.art-ea2f8fdeb28c42799228d559b21a2a93 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:07:02Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ea2f8fdeb28c42799228d559b21a2a932023-01-22T04:40:58ZengElsevieriScience2589-00422023-01-01261105784THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rateMareike Polenkowski0Aldrige Bernardus Allister1Sebastian Burbano de Lara2Andrew Pierce3Bethany Geary4Omar El Bounkari5Lutz Wiehlmann6Andrea Hoffmann7Anthony D. Whetton8Teruko Tamura9Doan Duy Hai Tran10Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover D-30623, Germany; Institut für Zellbiochemie, Medizinische Hochschule Hannover, Hannover D-30623, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover D-30623, Germany; Institut für Humangenetik, Medizinische Hochschule Hannover, Hannover D-30623, GermanyGerman Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyStem Cell and Leukemia Protoemics Laboratory, University of Manchester, Manchester M20 3LJ, UKStem Cell and Leukemia Protoemics Laboratory, University of Manchester, Manchester M20 3LJ, UKInstitute for Stroke and Dementia Research, Ludwig-Maximilians-Universität, 81377 Munich, GermanyPädiatrische Pneumologie Hannover Medical School, Hannover D-30623, GermanyDepartment of Orthopedic Surgery, Hannover Medical School, Hannover D-30623, GermanyStoller Biomarker Discovery Centre, University of Manchester, Manchester M13 9PL, UKInstitut für Zellbiochemie, Medizinische Hochschule Hannover, Hannover D-30623, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover D-30623, Germany; Institut für Zellbiochemie, Medizinische Hochschule Hannover, Hannover D-30623, Germany; Corresponding authorSummary: THOC5, a member of the THO complex, is essential for the 3′processing of some inducible genes, the export of a subset of mRNAs and stem cell survival. Here we show that THOC5 depletion results in altered 3′cleavage of >50% of mRNAs and changes in RNA polymerase II binding across genes. THOC5 is recruited close to high-density polymerase II sites, suggesting that THOC5 is involved in transcriptional elongation. Indeed, measurement of elongation rates in vivo demonstrated decreased rates in THOC5-depleted cells. Furthermore, THOC5 is preferentially recruited to its target genes in slow polymerase II cells compared with fast polymerase II cells. Importantly chromatin-associated THOC5 interacts with CDK12 (a modulator of transcription elongation) and RNA helicases DDX5, DDX17, and THOC6 only in slow polymerase II cells. The CDK12/THOC5 interaction promotes CDK12 recruitment to R-loops in a THOC6-dependent manner. These data demonstrate a novel function of THOC5 in transcription elongation.http://www.sciencedirect.com/science/article/pii/S2589004222020570Molecular biologyCell biology |
| spellingShingle | Mareike Polenkowski Aldrige Bernardus Allister Sebastian Burbano de Lara Andrew Pierce Bethany Geary Omar El Bounkari Lutz Wiehlmann Andrea Hoffmann Anthony D. Whetton Teruko Tamura Doan Duy Hai Tran THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate iScience Molecular biology Cell biology |
| title | THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate |
| title_full | THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate |
| title_fullStr | THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate |
| title_full_unstemmed | THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate |
| title_short | THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate |
| title_sort | thoc5 complexes with ddx5 ddx17 and cdk12 to regulate r loop structures and transcription elongation rate |
| topic | Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222020570 |
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