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首页> 外文期刊>Frontiers in Molecular Neuroscience >Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1
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Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

机译:转录后调节剂Cpeb1对成人中枢神经系统轴突再生的调节。

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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 na?ve 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.
机译:轴突损伤后,成年哺乳动物中枢神经系统(CNS)神经元无法再生,从而导致永久性功能障碍。然而,这种再生失败的原因尚不完全清楚。在这里,我们研究了脊髓损伤后不久的转录组和翻译组。损伤和幼稚脊髓中总RNA和核糖体结合RNA的分析表明,转录后的基因表达调控非常重要。特别是,与神经系统发育相关的转录本在总RNA组分中被下调,同时保持稳定地加载到核糖体上。有趣的是,转录后调节的转录物的基序关联分析确定,胞质聚腺苷酸化元件(CPE)富含这些转录物的一个子集,在转录组水平上更能抵抗损伤诱导的还原。通过在小鼠和果蝇中枢神经系统神经元中CPE结合蛋白Cpeb1的过表达来调节这些转录本,促进损伤后的轴突再生。我们的研究发现了增强受损的中枢神经轴突再生的全球进化保守转录后机制。

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