The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking
Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT...
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Taylor & Francis Group
2024-12-01
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Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2023.2294222 |
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author | Daniel P. Neumann Katherine A. Pillman B. Kate Dredge Andrew G. Bert Caroline A. Phillips Rachael Lumb Yesha Ramani Cameron P. Bracken Brett G. Hollier Luke A. Selth Traude H. Beilharz Gregory J. Goodall Philip A. Gregory |
author_facet | Daniel P. Neumann Katherine A. Pillman B. Kate Dredge Andrew G. Bert Caroline A. Phillips Rachael Lumb Yesha Ramani Cameron P. Bracken Brett G. Hollier Luke A. Selth Traude H. Beilharz Gregory J. Goodall Philip A. Gregory |
author_sort | Daniel P. Neumann |
collection | DOAJ |
description | Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3’ end anchored RNA sequencing, we mapped the alternative polyadenylation (APA) landscape following Transforming Growth Factor (TGF)-β-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3’UTR lengthening during this cell state transition. Investigation of potential mediators of APA indicated the RNA-binding protein Quaking (QKI), a splicing factor induced during EMT, regulates a subset of events including the length of its own transcript. Analysis of QKI crosslinked immunoprecipitation (CLIP)-sequencing data identified the binding of QKI within 3’ untranslated regions (UTRs) was enriched near cleavage and polyadenylation sites. Following QKI knockdown, APA of many transcripts is altered to produce predominantly shorter 3’UTRs associated with reduced gene expression. These findings reveal the changes in APA that occur during EMT and identify a potential role for QKI in this process. |
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institution | Kabale University |
issn | 1547-6286 1555-8584 |
language | English |
publishDate | 2024-12-01 |
publisher | Taylor & Francis Group |
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series | RNA Biology |
spelling | doaj-art-f948ce2e7da94619a7c424e6a9a539bd2025-02-05T05:42:21ZengTaylor & Francis GroupRNA Biology1547-62861555-85842024-12-0121119920910.1080/15476286.2023.2294222The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein QuakingDaniel P. Neumann0Katherine A. Pillman1B. Kate Dredge2Andrew G. Bert3Caroline A. Phillips4Rachael Lumb5Yesha Ramani6Cameron P. Bracken7Brett G. Hollier8Luke A. Selth9Traude H. Beilharz10Gregory J. Goodall11Philip A. Gregory12Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaAustralian Prostate Cancer Research Centre - Queensland, Centre for Genomics and Personalised Health, Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, AustraliaFaculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, AustraliaDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaEpithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3’ end anchored RNA sequencing, we mapped the alternative polyadenylation (APA) landscape following Transforming Growth Factor (TGF)-β-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3’UTR lengthening during this cell state transition. Investigation of potential mediators of APA indicated the RNA-binding protein Quaking (QKI), a splicing factor induced during EMT, regulates a subset of events including the length of its own transcript. Analysis of QKI crosslinked immunoprecipitation (CLIP)-sequencing data identified the binding of QKI within 3’ untranslated regions (UTRs) was enriched near cleavage and polyadenylation sites. Following QKI knockdown, APA of many transcripts is altered to produce predominantly shorter 3’UTRs associated with reduced gene expression. These findings reveal the changes in APA that occur during EMT and identify a potential role for QKI in this process.https://www.tandfonline.com/doi/10.1080/15476286.2023.2294222Quakingepithelial-mesenchymal transitionalternative polyadenylationCrosslinked immunopreciptation (CLIP) sequencing3’ untranslated region (3’UTR)RNA binding protein (RBP) |
spellingShingle | Daniel P. Neumann Katherine A. Pillman B. Kate Dredge Andrew G. Bert Caroline A. Phillips Rachael Lumb Yesha Ramani Cameron P. Bracken Brett G. Hollier Luke A. Selth Traude H. Beilharz Gregory J. Goodall Philip A. Gregory The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking RNA Biology Quaking epithelial-mesenchymal transition alternative polyadenylation Crosslinked immunopreciptation (CLIP) sequencing 3’ untranslated region (3’UTR) RNA binding protein (RBP) |
title | The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking |
title_full | The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking |
title_fullStr | The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking |
title_full_unstemmed | The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking |
title_short | The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking |
title_sort | landscape of alternative polyadenylation during emt and its regulation by the rna binding protein quaking |
topic | Quaking epithelial-mesenchymal transition alternative polyadenylation Crosslinked immunopreciptation (CLIP) sequencing 3’ untranslated region (3’UTR) RNA binding protein (RBP) |
url | https://www.tandfonline.com/doi/10.1080/15476286.2023.2294222 |
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