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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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:RNA Biology
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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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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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