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微小 RNA 与学习、记忆及神经疾病。

MicroRNAs in learning, memory, and neurological diseases.

机构信息

Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

出版信息

Learn Mem. 2012 Aug 16;19(9):359-68. doi: 10.1101/lm.026492.112.

DOI:10.1101/lm.026492.112
PMID:22904366
Abstract

MicroRNAs (miRNAs) represent a class of small regulatory noncoding RNAs ∼22 bp in length that mediate post-transcriptional silencing of gene expression via the recognition of specific sequences in target messenger (m)RNAs. The current body of literature suggests that miRNAs are fine-tuning regulators of gene expression profiles in a wide range of biological processes, from development to cancer. Many miRNAs are highly expressed in the adult nervous system in a spatially and temporally controlled manner in normal physiology, as well as in certain pathological conditions. These findings emphasize that gene regulation networks based on miRNA activities may be particularly important to brain function, and that perturbation of these networks may result in abnormal brain function. Indeed, miRNAs have been implicated in various aspects of dendrite remodeling and synaptic plasticity, as well as in experience-dependent adaptive changes of neural circuits in the postnatal developmental and adult brain. Recent advances in methods of next-generation sequencing, such as RNA-seq, offer the means to quantitatively evaluate the functions of miRNAs in a genome-wide manner in large cohorts of samples. These new technologies have already yielded valuable information and are expanding our understanding of miRNA-based mechanisms in higher-order brain processing, including learning and memory and cognition, as well as in neuropsychiatric disorders.

摘要

微小 RNA(miRNAs)是一类长度约为 22 个碱基的小调控性非编码 RNA,通过识别靶信使(m)RNA 中的特定序列,介导基因表达的转录后沉默。目前的文献表明,miRNAs 是从发育到癌症等广泛生物过程中基因表达谱的精细调节因子。在正常生理和某些病理条件下,许多 miRNA 以时空控制的方式在成年神经系统中高度表达。这些发现强调了基于 miRNA 活性的基因调控网络可能对大脑功能特别重要,并且这些网络的扰动可能导致大脑功能异常。事实上,miRNAs 已经涉及树突重塑和突触可塑性的各个方面,以及在出生后发育和成年大脑中神经回路的经验依赖性适应性变化。下一代测序方法(如 RNA-seq)的最新进展为在大量样本中以全基因组的方式定量评估 miRNA 的功能提供了手段。这些新技术已经提供了有价值的信息,并扩展了我们对高级大脑处理中基于 miRNA 的机制的理解,包括学习、记忆和认知,以及神经精神障碍。

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