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miRNAs 对基因表达的转录后调控

Post-transcriptional stimulation of gene expression by microRNAs.

机构信息

Harvard Medical School, Boston, MA, USA.

出版信息

Adv Exp Med Biol. 2013;768:97-126. doi: 10.1007/978-1-4614-5107-5_7.

Abstract

MicroRNAs are small noncoding RNA regulatory molecules that control gene expression by guiding associated effector complexes to other RNAs via sequence-specific recognition of target sites. Misregulation of microRNAs leads to a wide range of diseases including cancers, inflammatory and developmental disorders. MicroRNAs were found to mediate deadenylation-dependent decay and translational repression of messages through partially complementary microRNA target sites in the 3'-UTR (untranslated region). A growing series of studies has demonstrated that microRNAs and their associated complexes (microRNPs) elicit alternate functions that enable stimulation of gene expression in addition to their assigned repressive roles. These reports, discussed in this chapter, indicate that microRNA-mediated effects via natural 3' and 5'-UTRs can be selective and controlled, dictated by the RNA sequence context, associated complex, and cellular conditions. Similar to the effects of repression, upregulated gene expression by microRNAs varies from small refinements to significant amplifications in expression. An emerging theme from this literature is that microRNAs have a versatile range of abilities to manipulate post-transcriptional control mechanisms leading to controlled gene expression. These studies reveal new potentials for microRNPs in gene expression control that develop as responses to specific cellular conditions.

摘要

微小 RNA 是一种小的非编码 RNA 调控分子,通过与靶位点的序列特异性识别,引导相关效应复合物到其他 RNA 上,从而控制基因表达。微小 RNA 的失调会导致广泛的疾病,包括癌症、炎症和发育障碍。研究发现,微小 RNA 通过在 3'UTR(非翻译区)中与靶位点的部分互补来介导依赖脱腺苷酸化的衰减和翻译抑制。越来越多的研究表明,微小 RNA 及其相关复合物(miRNPs)发挥替代功能,除了其抑制作用外,还能刺激基因表达。本章讨论的这些报告表明,通过天然的 3'和 5'UTR 进行的微小 RNA 介导的效应可以是选择性和可控的,由 RNA 序列上下文、相关复合物和细胞条件决定。与抑制作用相似,微小 RNA 上调基因表达的程度从微小的细化到显著的表达放大。从这些文献中出现的一个新主题是,微小 RNA 具有多种能力来操纵转录后控制机制,从而实现对基因表达的控制。这些研究揭示了 microRNPs 在基因表达控制方面的新潜力,这些潜力是作为对特定细胞条件的反应而发展起来的。

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