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哺乳动物学习和记忆中的转录后调控作用。

Role of Post-Transcriptional Regulation in Learning and Memory in Mammals.

机构信息

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128 Palermo, Italy.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy.

出版信息

Genes (Basel). 2024 Mar 5;15(3):337. doi: 10.3390/genes15030337.

Abstract

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is of the most importance in the brain, where all the steps of mRNA maturation, transport to different regions of the cells and actual expression, in response to specific signals, constitute the molecular basis for neuronal plasticity and, as a consequence, for structural stabilization/modification of synapses; notably, these latter events are fundamental for the highest brain functions, such as learning and memory, and are characterized by long-term potentiation (LTP) of specific synapses. Here, we will discuss the molecular bases of these fundamental events by considering both the role of RNA-binding proteins (RBPs) and the effects of non-coding RNAs involved in controlling splicing, editing, stability and translation of mRNAs. Importantly, it has also been found that dysregulation of mRNA metabolism/localization is involved in many pathological conditions, arising either during brain development or in the adult nervous system.

摘要

经过几十年的时间,大多数关于基因表达调控的分子研究都集中在转录事件上,人们逐渐认识到,为了确定何时何地合成特定的蛋白质,转录后调控同样重要。在大脑中,翻译调控最为重要,其中 mRNA 成熟、向细胞不同区域的运输以及对特定信号的实际表达等所有步骤,构成了神经元可塑性的分子基础,进而导致了突触的结构稳定/修饰;值得注意的是,这些后一事件是大脑最高功能(如学习和记忆)的基础,其特征是特定突触的长时程增强(LTP)。在这里,我们将通过考虑 RNA 结合蛋白 (RBPs) 的作用以及参与控制 mRNA 剪接、编辑、稳定性和翻译的非编码 RNA 的作用,来讨论这些基本事件的分子基础。重要的是,人们还发现,mRNA 代谢/定位的失调与许多病理状况有关,这些状况要么发生在大脑发育过程中,要么发生在成年神经系统中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4f8/10970538/cee6bd33528a/genes-15-00337-g001.jpg

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