Regulation of non-coding RNA networks in the nervous system--what's the REST of the story?
Regulation of non-coding RNA networks in the nervous system--what's the REST of the story?
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DOI：
10.1016/j.neulet.2009.07.093
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发表时间：
2009-12-04
影响因子：
2.5
通讯作者：
Mehler MF
中科院分区：
文献类型：
--
作者：
Qureshi IA;Mehler MF
最近的进展为揭示细胞复杂性、多样性和连通性如何在基因组内编码的机制提供了新的见解。抑制因子-1沉默转录因子/神经元限制性沉默因子（REST/NRSF）和非编码rna （ncRNAs）正在成为神经系统发育、体内平衡和可塑性几乎各个方面的关键调节因子。REST及其主要辅因子CoREST动态招募高延展性的大分子复合物到广泛分布的基因组调控序列中，包括抑制元件1/神经元限制性沉默元件（RE1/NRSE）。通过位点特异性靶向和高阶染色质重塑等表观遗传机制，REST和CoREST可以介导蛋白质编码基因和几种ncRNAs（如microRNAs [miRNAs]和long ncRNAs）的细胞类型和发育阶段特异性基因抑制、基因激活和长期基因沉默。反过来，这些ncrna同样涉及染色质结构和动力学、转录、转录后加工以及RNA编辑和运输的调节。此外，REST和CoREST的表达和功能受到上下文特异性转录和转录后机制的严格调控，包括与各种ncrna的双向反馈回路。毫不奇怪，REST和ncrna的解除管制都涉及从脑癌和中风到神经发育和神经退行性疾病等多种疾病的分子病理生理学。这篇综述总结了这些错综复杂的神经基因表达和功能控制系统之间复杂的机制关系的新兴方面。
Recent advances are now providing novel insights into the mechanisms that underlie how cellular complexity, diversity, and connectivity are encoded within the genome. The repressor element-1 silencing transcription factor / neuron-restrictive silencing factor (REST/NRSF) and non-coding RNAs (ncRNAs) are emerging as key regulators that seem to orchestrate almost every aspect of nervous system development, homeostasis, and plasticity. REST and its primary cofactor, CoREST, dynamically recruit highly malleable macromolecular complexes to widely distributed genomic regulatory sequences, including the repressor element 1 / neuron restrictive silencer element (RE1/NRSE). Through epigenetic mechanisms, such as site-specific targeting and higher-order chromatin remodeling, REST and CoREST can mediate cell type- and developmental stage-specific gene repression, gene activation, and long-term gene silencing for protein-coding genes and for several classes of ncRNAs (e.g. microRNAs [miRNAs] and long ncRNAs). In turn, these ncRNAs have similarly been implicated in the regulation of chromatin architecture and dynamics, transcription, post-transcriptional processing, and RNA editing and trafficking. In addition, REST and CoREST expression and function are tightly regulated by context-specific transcriptional and post-transcriptional mechanisms including bidirectional feedback loops with various ncRNAs. Not surprisingly, deregulation of REST and ncRNAs are both implicated in the molecular pathophysiology underlying diverse disorders that range from brain cancer and stroke to neurodevelopmental and neurodegenerative diseases. This review summarizes emerging aspects of the complex mechanistic relationships between these intricately interlaced control systems for neural gene expression and function.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
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DOI：
10.1073/pnas.96.17.9873
发表时间：
1999-08-17
影响因子：
11.1
作者：
Andrés, ME;Burger, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
5.3
作者：
Auboeuf, D;Dowhan, DH;O'Malley, BW
通讯作者：
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影响因子：
9.8
作者：
Canzonetta, Claudia;Mulligan, Claire;Nizetic, Dean
通讯作者：
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