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Front Mol Neurosci. 2018 Jan 12;10:445. doi: 10.3389/fnmol.2017.00445. eCollection 2017.

Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1.

Author information

1
Division of Molecular Neurobiology, German Cancer Research Center, Heidelberg, Germany.
2
Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.
3
VIB Center for the Biology of Disease and Center for Human Genetics, VIB and KU Leuven, Leuven, Belgium.
4
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong.
5
Department of Neuroregeneration, University Hospital Heidelberg, Heidelberg, Germany.
6
Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
7
Zentrum für Molekulare Biologie, University of Heidelberg, Heidelberg, Germany.
8
Translational Control of Cell Cycle and Differentiation, Institute for Research in Biomedicine, Barcelona, Spain.
9
Virus Host Interaction, Heidelberg University Hospital, Center for Infectious Diseases/Virology, Cluster of Excellence CellNetworks, BioQuant, Heidelberg, Germany.
10
Center 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.
11
Sorbonne 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.

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:

CPEB1; axon regeneration; motif analysis; polysome profiling; spinal cord injuries; translation

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