Ji Sheng-Jian, Jaffrey Samie R
Department of Pharmacology, Weill Medical College, Cornell University, New York, New York, 10065.
Dev Neurobiol. 2014 Mar;74(3):245-58. doi: 10.1002/dneu.22112. Epub 2013 Sep 30.
Developing axons contain transcripts that are locally translated to influence the axonal proteome. Recent studies have shown that axonal transcripts include mRNAs encoding transcription factors. These mRNAs are translated to produce transcription factors that can be retrogradely trafficked back to the nucleus, where they regulate gene expression programs. These findings point to a novel mechanism of growth cone-to-nucleus signaling that occurs when growth cones encounter extracellular signaling molecules that stimulate local translation of these transcription factors, thereby influencing gene transcription. Here we summarize recent findings on local translation of transcription factors in axons and their roles in different neuronal processes such as neuronal specification, survival, and axon regeneration. Comprehensive axonal transcriptome studies have revealed transcripts that encode many more transcription factors and cofactors, suggesting a potentially broad role for this type of signaling. We review the progress on the approaches and tools that have been developed to study local translation and retrograde trafficking of transcription factors. We also highlight the challenges in the field and discuss the potential routes to resolving them.
正在发育的轴突含有可进行局部翻译以影响轴突蛋白质组的转录本。最近的研究表明，轴突转录本包括编码转录因子的mRNA。这些mRNA被翻译以产生转录因子，这些转录因子可逆行运输回细胞核，在那里它们调节基因表达程序。这些发现指出了一种新的生长锥到细胞核的信号传导机制，当生长锥遇到刺激这些转录因子局部翻译的细胞外信号分子时就会发生这种机制，从而影响基因转录。在这里，我们总结了关于轴突中转录因子局部翻译及其在不同神经元过程（如神经元特化、存活和轴突再生）中的作用的最新发现。全面的轴突转录组研究揭示了编码更多转录因子和辅助因子的转录本，表明这种信号传导类型可能具有广泛的作用。我们回顾了为研究转录因子的局部翻译和逆行运输而开发的方法和工具的进展。我们还强调了该领域的挑战，并讨论了解决这些挑战的潜在途径。
