Frontiers in Molecular Neuroscience (Jan 2018)
Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1
- Wilson Pak-Kin Lou,
- Wilson Pak-Kin Lou,
- Alvaro Mateos,
- Marta Koch,
- Stefan Klussman,
- Stefan Klussman,
- Chao Yang,
- Na Lu,
- Sachin Kumar,
- Sachin Kumar,
- Stefanie Limpert,
- Manuel Göpferich,
- Manuel Göpferich,
- Marlen Zschaetzsch,
- Christopher Sliwinski,
- Marc Kenzelmann,
- Matthias Seedorf,
- Carlos Maillo,
- Elena Senis,
- Dirk Grimm,
- Radhika Puttagunta,
- Raul Mendez,
- Kai Liu,
- Kai Liu,
- Bassem A. Hassan,
- Bassem A. Hassan,
- Ana Martin-Villalba
Affiliations
- Wilson Pak-Kin Lou
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- Wilson Pak-Kin Lou
- Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany
- Alvaro Mateos
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- Marta Koch
- VIB Center for the Biology of Disease and Center for Human Genetics, VIB and KU Leuven, Leuven, Belgium
- Stefan Klussman
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- Stefan Klussman
- Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany
- Chao Yang
- Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
- Na Lu
- Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
- Sachin Kumar
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- Sachin Kumar
- Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany
- Stefanie Limpert
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- Manuel Göpferich
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- Manuel Göpferich
- Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany
- Marlen Zschaetzsch
- VIB Center for the Biology of Disease and Center for Human Genetics, VIB and KU Leuven, Leuven, Belgium
- Christopher Sliwinski
- Department of Neuroregeneration, University Hospital Heidelberg, Heidelberg, Germany
- Marc Kenzelmann
- Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany
- Matthias Seedorf
- Zentrum für Molekulare Biologie, University of Heidelberg, Heidelberg, Germany
- Carlos Maillo
- Translational Control of Cell Cycle and Differentiation, Institute for Research in Biomedicine, Barcelona, Spain
- Elena Senis
- Virus Host Interaction, Heidelberg University Hospital, Center for Infectious Diseases/Virology, Cluster of Excellence CellNetworks, BioQuant, Heidelberg, Germany
- Dirk Grimm
- Virus Host Interaction, Heidelberg University Hospital, Center for Infectious Diseases/Virology, Cluster of Excellence CellNetworks, BioQuant, Heidelberg, Germany
- Radhika Puttagunta
- Department of Neuroregeneration, University Hospital Heidelberg, Heidelberg, Germany
- Raul Mendez
- Translational Control of Cell Cycle and Differentiation, Institute for Research in Biomedicine, Barcelona, Spain
- Kai Liu
- Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
- Kai Liu
- 0Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
- Bassem A. Hassan
- VIB Center for the Biology of Disease and Center for Human Genetics, VIB and KU Leuven, Leuven, Belgium
- Bassem A. Hassan
- 1Sorbonne Universités, UPMC Univ Paris 06, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut du Cerveau et de la Moelle epiniere - Hôpital Pitié-Salpêtrière, Paris, France
- Ana Martin-Villalba
- Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fnmol.2017.00445
- Journal volume & issue
-
Vol. 10
Abstract
Adult mammalian central nervous system (CNS) neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.
Keywords
