A deep dive into local mRNA translation in neurons.
A deep dive into local mRNA translation in neurons.
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深入研究神经元中的局部 mRNA 翻译。
DOI：
10.1073/pnas.2117116118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Klann,Eric
中科院分区：
文献类型：
--
作者：
Oliveira,MauricioM;Klann,Eric
神经元是古怪的细胞。由于它们的高度连接性，它们已经进化成细长的多室细胞。其中一个是突触，负责神经元间的连接，以便将信息从一个神经元传递到另一个神经元，并最终允许复杂的行为。每个突触末端都有自己的历史，由当地存在的蛋白质的可塑性组成所塑造。这种蛋白质库可以迅速改变以适应并使突触变强或变弱，这通常被称为突触可塑性。持久的突触可塑性需要从头开始蛋白质合成，但这仍然是一个相对快速的事件，需要突触前和突触后神经元立即做出反应以确保成功，如果神经元必须在其索马中产生蛋白质，然后将其发送到树突和轴突终末，那么这似乎是不可能的。这个难题导致了一个有趣的假设，该假设认为神经元不仅将蛋白质运输到远处的树突和轴突末端，而且还可以翻译储存在这些隔室中等待翻译的精确时刻的信使RNA（mRNA）（1）。这个假设引发了新的问题，其中最有趣的是，这些mRNA的身份是什么，它们与神经元索马中翻译的mRNA有何不同？在PNAS中，Glock et al. (2)利用精细RNA测序（RNA-seq）技术来鉴定被发送到轴突和树突以进行翻译的mRNA，以及保留在索马中的mRNA。(2)使用了两种RNA测序技术的组合：总RNA-seq和核糖体分析（核糖体测序[Ribo-seq]）。前者识别所有存在于所分析结构中的RNA，而后者通过阅读结合在核糖体上的小部分mRNA来识别此时正在翻译的mRNA。为了确保他们能从
Neurons are quirky cells. Due to their high connectivity, they have evolved to be elongated, multicompartmental cells. One of these compartments is the synapse, which is responsible for interneuronal connections in order to transmit information from one neuron to another and, ultimately, allow for complex behaviors. Each synaptic terminal has its own history, shaped by the very malleable composition of proteins present locally. This pool of proteins can rapidly change to adapt and make a synapse either stronger or weaker, which is typically referred to as synaptic plasticity. Long-lasting synaptic plasticity requires de novo protein synthesis but is nonetheless a relatively rapid event that needs immediate responses from both presynaptic and postsynaptic neurons to ensure success, which seems unlikely if neurons have to produce proteins in their soma and then send them to dendrites and axon terminals. This conundrum led to a fascinating hypothesis, which posits that neurons not only transport proteins to distant dendrites and axon terminals but also can translate messenger RNAs (mRNAs) that are stored in these compartments awaiting the precise moment to be translated (1). New questions arose from this hypothesis, and one of the most intriguing was, What are the identities of these mRNAs, and how do they differ from the ones that are translated in the soma of neurons? In PNAS, Glock et al.(2) make use of refined RNA sequencing (RNA-seq) techniques to identify the mRNAs that are sent to axons and dendrites to be translated, as well as those that remain in the soma.To identify mRNAs in neuronal soma, Glock et al.(2) used the combination of two RNA sequencing techniques: total RNA-seq and ribosome profiling (ribosome sequencing [Ribo-seq]). The former identifies all the RNAs that are present in the structures analyzed, whereas the latter identifies mRNAs that are being translated at that very moment by reading small portions of mRNAs bound to the ribosomes. To ensure that they were isolating somas from