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巩固和翻译调控。

Consolidation and translation regulation.

机构信息

Sagol Department of Neurobiology, University of Haifa, Haifa 31905, Israel.

出版信息

Learn Mem. 2012 Aug 16;19(9):410-22. doi: 10.1101/lm.026849.112.

Abstract

mRNA translation, or protein synthesis, is a major component of the transformation of the genetic code into any cellular activity. This complicated, multistep process is divided into three phases: initiation, elongation, and termination. Initiation is the step at which the ribosome is recruited to the mRNA, and is regarded as the major rate-limiting step in translation, while elongation consists of the elongation of the polypeptide chain; both steps are frequent targets for regulation, which is defined as a change in the rate of translation of an mRNA per unit time. In the normal brain, control of translation is a key mechanism for regulation of memory and synaptic plasticity consolidation, i.e., the off-line processing of acquired information. These regulation processes may differ between different brain structures or neuronal populations. Moreover, dysregulation of translation leads to pathological brain function such as memory impairment. Both normal and abnormal function of the translation machinery is believed to lead to translational up-regulation or down-regulation of a subset of mRNAs. However, the identification of these newly synthesized proteins and determination of the rates of protein synthesis or degradation taking place in different neuronal types and compartments at different time points in the brain demand new proteomic methods and system biology approaches. Here, we discuss in detail the relationship between translation regulation and memory or synaptic plasticity consolidation while focusing on a model of cortical-dependent taste learning task and hippocampal-dependent plasticity. In addition, we describe a novel systems biology perspective to better describe consolidation.

摘要

mRNA 翻译,或蛋白质合成,是将遗传密码转化为任何细胞活动的主要组成部分。这个复杂的、多步骤的过程分为三个阶段:起始、延伸和终止。起始是核糖体被招募到 mRNA 的步骤,被认为是翻译的主要限速步骤,而延伸则由多肽链的延伸组成;这两个步骤都是调节的常见靶点,调节被定义为单位时间内 mRNA 翻译速率的变化。在正常大脑中,翻译的控制是调节记忆和突触可塑性巩固的关键机制,即获得信息的离线处理。这些调节过程可能在不同的脑结构或神经元群体中有所不同。此外,翻译的失调会导致记忆障碍等病理性脑功能。翻译机制的正常和异常功能都被认为会导致一组 mRNAs 的翻译上调或下调。然而,鉴定这些新合成的蛋白质,并确定在大脑的不同时间点、不同神经元类型和隔室中发生的蛋白质合成或降解的速率,需要新的蛋白质组学方法和系统生物学方法。在这里,我们详细讨论了翻译调节与记忆或突触可塑性巩固之间的关系,同时重点介绍了皮质依赖性味觉学习任务和海马依赖性可塑性的模型。此外,我们还描述了一种新的系统生物学视角,以更好地描述巩固。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc50/3418764/73651ebbe3fc/learnmem-026849f01.jpg

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