例如："lncRNA", "apoptosis", "WRKY"

Transcriptome 3'end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma.

Nat Commun. 2018 Dec 14;9(1):5331
Anton Ogorodnikov 1 , Michal Levin 2 , Surendra Tattikota 2 , Sergey Tokalov 2 , Mainul Hoque 3 , Denise Scherzinger 4 , Federico Marini 4 , Ansgar Poetsch 5 , Harald Binder 6 , Stephan Macher-Göppinger 7 , Hans Christian Probst 8 , Bin Tian 3 , Michael Schaefer 9 , Karl J Lackner 10 , Frank Westermann 11 , Sven Danckwardt 12
Anton Ogorodnikov 1 , Michal Levin 2 , Surendra Tattikota 2 , Sergey Tokalov 2 , Mainul Hoque 3 , Denise Scherzinger 4 , Federico Marini 4 , Ansgar Poetsch 5 , Harald Binder 6 , Stephan Macher-Göppinger 7 , Hans Christian Probst 8 , Bin Tian 3 , Michael Schaefer 9 , Karl J Lackner 10 , Frank Westermann 11 , Sven Danckwardt 12
+ et al

[No authors listed]

Author information
  • 1 McManus Laboratory, University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
  • 2 Centre for Thrombosis and Haemostasis (CTH), University Medical Centre Mainz, Mainz, 55131, Germany.
  • 3 Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.
  • 4 Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre Mainz, Mainz, 55131, Germany.
  • 5 School of Biomedical & Healthcare Sciences, Plymouth University, Plymouth, PL4 8AA, United Kingdom.
  • 6 Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, 79104, Germany.
  • 7 Institute for Pathology, University Medical Centre Mainz, Mainz, 55131, Germany.
  • 8 Research Center for Immunotherapy (FZI), University Medical Centre Mainz, Mainz, 55131, Germany.
  • 9 Department of Anaesthesiology and Research Centre Translational Neurosciences, University Medical Centre Mainz, Mainz, 55131, Germany.
  • 10 Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Mainz, 55131, Germany.
  • 11 Division of Neuroblastoma Genomics, German Cancer Research Centre (DKFZ), Heidelberg, 69120, Germany.
  • 12 German Centre for Cardiovascular Research (DZHK), Mainz, 55131, Germany. Sven.Danckwardt@unimedizin-mainz.de.

摘要

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 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 and an APA-network map with regulatory hubs.

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