Buchanan Isla M, Smith Trevor M, Gerber André P, Seibt Julie
Integrated Master Programme in Biochemistry, University of Surrey, Guildford, United Kingdom.
Department of Microbial Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
Front Mol Biosci. 2022 Oct 6;9:1008921. doi: 10.3389/fmolb.2022.1008921. eCollection 2022.
The regulation of mRNA translation plays an essential role in neurons, contributing to important brain functions, such as brain plasticity and memory formation. Translation is conducted by ribosomes, which at their core consist of ribosomal proteins (RPs) and ribosomal RNAs. While translation can be regulated at diverse levels through global or mRNA-specific means, recent evidence suggests that ribosomes with distinct configurations are involved in the translation of different subsets of mRNAs. However, whether and how such proclaimed ribosome heterogeneity could be connected to neuronal functions remains largely unresolved. Here, we postulate that the existence of heterologous ribosomes within neurons, especially at discrete synapses, subserve brain plasticity. This hypothesis is supported by recent studies in rodents showing that heterogeneous RP expression occurs in dendrites, the compartment of neurons where synapses are made. We further propose that sleep, which is fundamental for brain plasticity and memory formation, has a particular role in the formation of heterologous ribosomes, specialised in the translation of mRNAs specific for synaptic plasticity. This aspect of our hypothesis is supported by recent studies showing increased translation and changes in RP expression during sleep after learning. Thus, certain RPs are regulated by sleep, and could support different sleep functions, in particular brain plasticity. Future experiments investigating cell-specific heterogeneity in RPs across the sleep-wake cycle and in response to different behaviour would help address this question.
mRNA翻译的调控在神经元中起着至关重要的作用,有助于实现重要的脑功能,如脑可塑性和记忆形成。翻译由核糖体进行,核糖体的核心由核糖体蛋白(RPs)和核糖体RNA组成。虽然翻译可以通过全局或mRNA特异性方式在不同水平上受到调控,但最近的证据表明,具有不同构象的核糖体参与了不同mRNA子集的翻译。然而,这种所谓的核糖体异质性是否以及如何与神经元功能相关联,在很大程度上仍未得到解决。在这里,我们推测神经元内,尤其是在离散突触处存在异源核糖体,有助于脑可塑性。这一假设得到了最近在啮齿动物中的研究支持,这些研究表明异质RP表达发生在树突中,即形成突触的神经元区域。我们进一步提出,睡眠对脑可塑性和记忆形成至关重要,在异源核糖体的形成中具有特殊作用,这些异源核糖体专门用于翻译对突触可塑性特异的mRNA。我们假设的这一方面得到了最近研究的支持,这些研究表明学习后睡眠期间翻译增加以及RP表达发生变化。因此,某些RPs受睡眠调控,并可能支持不同的睡眠功能,特别是脑可塑性。未来研究跨睡眠-觉醒周期以及对不同行为做出反应时RPs细胞特异性异质性的实验,将有助于解决这个问题。