Biomedical Center (BMC), Division of Anatomy and Cell Biology, Ludwig-Maximilians-Universität, Planegg-Martinsried, Germany.
Biomedical Center (BMC), Division of Anatomy and Cell Biology, Ludwig-Maximilians-Universität, Planegg-Martinsried, Germany.
Trends Genet. 2016 Dec;32(12):788-800. doi: 10.1016/j.tig.2016.10.004. Epub 2016 Nov 4.
Local protein expression at synapses is a prerequisite for learning in mammalian neurons. It has been shown that a subset of RNAs is localized in dendrites. These transcripts are first assembled into ribonucleoprotein particles in the cell body and are then transported along the cytoskeleton to or near synapses in a translationally repressed state. However, we know very little about the underlying mechanisms of local translation as well as potential protein degradation. Research in the last years showed many features of general translation. One very interesting aspect with raising attention is co-translational folding, a process that guides protein folding during ribosome elongation. In this review, we propose that translation speed is influenced by the codon usage of localized transcripts, which in turn affects protein folding and ultimately degradation efficiency. Together, these processes significantly contribute to synaptic proteome changes and synaptic plasticity. Furthermore, we envision that co-translational misfolding could contribute to neurodegenerative diseases.
突触处的局部蛋白表达是哺乳动物神经元学习的前提。已经表明，一小部分 RNA 存在于树突中。这些转录本首先在细胞体中组装成核糖核蛋白颗粒，然后沿着细胞骨架运输到或靠近突触，处于翻译抑制状态。然而，我们对局部翻译的潜在机制以及潜在的蛋白质降解知之甚少。过去几年的研究显示了许多普遍翻译的特征。一个引起关注的非常有趣的方面是共翻译折叠，这是一个在核糖体延伸过程中指导蛋白质折叠的过程。在这篇综述中，我们提出翻译速度受局部转录本密码子使用的影响，这反过来又影响蛋白质折叠，最终影响降解效率。这些过程共同显著影响突触蛋白质组的变化和突触可塑性。此外，我们设想共翻译错误折叠可能导致神经退行性疾病。
