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

Frontiers in Molecular Neuroscience, 2018 · DOI: 10.3389/fnmol.2017.00445 · Published: January 12, 2018

Regenerative Medicine Neurology Genetics

Simple Explanation

Adult mammalian central nervous system (CNS) neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. The study investigates post-transcriptional regulation of gene expression after spinal cord injury. The study found that transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes, suggesting a post-transcriptional regulatory mechanism. Overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury, uncovering a global evolutionarily conserved post-transcriptional mechanism.

Study Duration

Not specified

Participants

Mice and Drosophila

Evidence Level

Level: Not specified, Study type: Molecular and genetic analysis, animal models

Key Findings

1
A substantial post-transcriptional regulation of gene expression occurs following spinal cord injury.
2
The cytoplasmic polyadenylation element (CPE) is enriched in a subset of transcripts that are more resistant to injury-induced reduction at the transcriptome level.
3
Overexpression of Cpeb1 in mouse and Drosophila CNS neurons promotes axonal regeneration following injury.

Research Summary

This study proﬁled the responses to spinal cord injury both at transcriptome and translatome level, and ﬁnd them to be highly uncoupled, highlighting the importance of post-transcriptional gene regulation in axon regeneration. A screening of uncoupled factors in Drosophila sLNvs revealed that 50% of the transcripts being prioritized for translation despite exhibiting reduced levels following spinal injury modulated axonal growth of developing neurons in the ﬂy. CPEB1 emerged as a conserved necessary and suﬃcient activator of neuronal regeneration, illustrating the feasibility of uncovering novel functions of RNA-regulatory proteins.

Practical Implications

Therapeutic Potential

Targeting Cpeb1 and CPE-mediated pathways could offer new therapeutic strategies for promoting axonal regeneration after CNS injuries.

Understanding Regeneration Failure

The study sheds light on why adult mammalian CNS neurons fail to regenerate after injury, providing insights into the molecular mechanisms that need to be activated for successful regeneration.

Conserved Mechanisms

The identification of a conserved post-transcriptional mechanism enhances the understanding of axonal de/regeneration across different models and species, allowing for more effective translational research.

Study Limitations

1
The study focuses on a single time point (9 hours) after injury, which may not capture the full spectrum of post-transcriptional regulation.
2
The exact mechanisms by which Cpeb1 promotes axonal regeneration remain to be fully elucidated.
3
The complexity of Cpeb1 functions depending of the context

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