Transcriptome 3′end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma
Abstract: Diversification at the transcriptome 3′end is an important and evolutionarily conserved layer of gene regulation associated with differentiation and dedifferentiation processes. Here, we identify extensive transcriptome 3′end-alterations in neuroblastoma, a tumour entity with a paucity of recurrent somatic mutations and an unusually high frequency of spontaneous regression. Utilising extensive RNAi-screening we reveal the landscape and drivers of transcriptome 3′end-diversification, discovering PCF11 as critical regulator, directing alternative polyadenylation (APA) of hundreds of transcripts including a differentiation RNA-operon. PCF11 shapes inputs converging on WNT-signalling, and governs cell cycle, proliferation, apoptosis and neurodifferentiation. Postnatal PCF11 down-regulation induces a neurodifferentiation program, and low-level PCF11 in neuroblastoma associates with favourable outcome and spontaneous tumour regression. Our findings document a critical role for APA in tumorigenesis and describe a novel mechanism for cell fate reprogramming in neuroblastoma with potentially important clinical implications. We provide an interactive data repository of transcriptome-wide APA covering > 170 RNAis, and an APA-network map with regulatory hubs
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature communications. - 9, 1 (2018) , 5331, ISSN: 2041-1723
- Ereignis
-
Veröffentlichung
- (wo)
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Freiburg
- (wer)
-
Universität
- (wann)
-
2019
- Urheber
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Ogorodnikov, Anton
Levin, Michal
Tattikota, Surendra
Tokalov, Sergey
Hoque, Mainul
Scherzinger, Denise
Marini, Federico
Poetsch, Ansgar
Binder, Harald
Macher-Göppinger, Stephan
Probst, Hans Christian
Tian, Bin
Schäfer, Michael K. E.
Lackner, Karl J.
Westermann, Frank
Danckwardt, Sven
- DOI
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10.1038/s41467-018-07580-5
- URN
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urn:nbn:de:bsz:25-freidok-1479637
- Rechteinformation
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
25.03.2025, 13:48 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Ogorodnikov, Anton
- Levin, Michal
- Tattikota, Surendra
- Tokalov, Sergey
- Hoque, Mainul
- Scherzinger, Denise
- Marini, Federico
- Poetsch, Ansgar
- Binder, Harald
- Macher-Göppinger, Stephan
- Probst, Hans Christian
- Tian, Bin
- Schäfer, Michael K. E.
- Lackner, Karl J.
- Westermann, Frank
- Danckwardt, Sven
- Universität
Entstanden
- 2019
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