Regulation of adult CNS axonal regeneration by the post-transcriptional regulator Cpeb1
Adult mammalian 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 study the transcriptome and translatome shortly after spinal cord injury. Profiling of t...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 January 2018
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| In: |
Frontiers in molecular neuroscience
Year: 2018, Volume: 10 |
| ISSN: | 1662-5099 |
| DOI: | 10.3389/fnmol.2017.00445 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.3389/fnmol.2017.00445 Verlag, Volltext: https://www.frontiersin.org/articles/10.3389/fnmol.2017.00445/full 
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| Author Notes: | Wilson Pak-Kin Lou, Alvaro Mateos, Marta Koch, Stefan Klussman, Chao Yang, Na Lu, Sachin Kumar, Stefanie Limpert, Manuel Göpferich, Marlen Zschaetzsch, Christopher Sliwinski, Marc Kenzelmann, Matthias Seedorf, Carlos Maillo, Elena Senis, Dirk Grimm, Radhika Puttagunta, Raul Mendez, Kai Liu, Bassem A. Hassan and Ana Martin-Villalba |
| Summary: | Adult mammalian 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 study the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identify 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 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 uncovers a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons. |
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| Item Description: | Gesehen am 15.10.2018 Accepted: 20 December 2017 |
| Physical Description: | Online Resource |
| ISSN: | 1662-5099 |
| DOI: | 10.3389/fnmol.2017.00445 |