Epigenetic Control of MicroRNA Expression and Aging.
Epigenetic Control of MicroRNA Expression and Aging.
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DOI：
10.2174/138920209788185225
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发表时间：
2009-05
期刊：
影响因子：
2.6
通讯作者：
Wang E
中科院分区：
文献类型：
--
作者：
Liang R;Bates DJ;Wang E
MicroRNA是非编码RNA中的一个主要类别，通过降解靶信息或抑制其翻译，在转录后水平负调控基因表达。microRNA可以被称为基因表达的“调光开关”，因为它们能够抑制基因表达而不完全沉默它。无论是通过上调特定的microRNA组来抑制不需要的基因表达，还是通过下调其他microRNA，其靶基因的表达是细胞功能所必需的，如细胞增殖，凋亡或分化，这些调节RNA在多种细胞过程中起关键作用。这两组microRNA表达之间的平衡在很大程度上决定了特定细胞类型的功能。我们最近对几个模型系统的研究结果表明，随着年龄的增长，microRNA表达有上调的趋势，伴随着靶基因的反向下调。本文综述了可能为这种上调趋势提供潜在控制的分子机制，重点关注各种microRNA自身启动子的激活，通过与关键转录因子的结合，应激反应，成簇DNA结构域的甲基化等。因此，衰老的表观基因组控制可能部分是由于不需要的microRNA表达的启动子激活增强，从而下调其靶基因产物。覆盖和抑制这些非编码RNA的激活可能被证明是未来研究的新前沿，以延缓衰老和延长健康寿命。
MicroRNAs are a major category among the noncoding RNA fraction that negatively regulate gene expression at the post-transcriptional level, by either degrading the target messages or inhibiting their translation. MicroRNAs may be referred to as ‘dimmer switches’ of gene expression, because of their ability to repress gene expression without completely silencing it. Whether through up-regulating specific groups of microRNAs to suppress unwanted gene expressions, or by down-regulating other microRNAs whose target genes’ expression is necessary for cellular function, such as cell proliferation, apoptosis, or differentiation, these regulatory RNAs play pivotal roles in a wide variety of cellular processes. The equilibrium between these two groups of microRNA expressions largely determines the function of particular cell types. Our recent results with several model systems show that upon aging, there is a trend of up-regulation of microRNA expression, with concomitant inverse down-regulation of target genes. This review addresses molecular mechanisms that may provide the underlying control for this up-regulating trend, focusing on activation by various microRNAs’ own promoters, through binding with pivotal transcription factors, stress response, methylation of clustered DNA domains, etc. Thus, epigenomic control of aging may be due in part to heightened promoter activation of unwanted microRNA expressions, which in turn down-regulate their target gene products. Overriding and dampening the activation of these noncoding RNAs may prove to be a new frontier for future research, to delay aging and extend healthy life-span.
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DOI：
10.1073/pnas.0808830105
发表时间：
2008-10-21
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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影响因子：
56.9
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影响因子：
11.2
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