Transcriptional gene silencing in humans.
Transcriptional gene silencing in humans.
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DOI：
10.1093/nar/gkw139
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发表时间：
2016-08-19
影响因子：
14.9
通讯作者：
Morris KV
中科院分区：
文献类型：
--
作者：
Weinberg MS;Morris KV
自从首次观察到小的非编码RNA可以在功能上调节人类细胞中的表观遗传状态以实现功能性转录基因沉默（TGS）以来，已经过去了十多年。TGS在机制上不同于RNA干扰（RNAi）基因沉默途径。TGS可以导致基因表达的长期稳定的表观遗传修饰，这些修饰可以在细胞分裂期间传递给子细胞，而RNAi则不能。TGS的早期研究在很大程度上被忽视，随后发现的小RNA指导的post-TGS和RNAi掩盖了这一点。最近在人类细胞中发现内源性长非编码RNA的功能是调节表观基因组，这引起了对早期工作的重新评价。在小的和长的非编码RNA转录调控机制中涉及的蛋白质之间存在明显的和共同的重叠，这表明使用小的非编码RNA来调节转录的早期研究利用了先前未被识别的RNA指导的基因调控的内源性机制。在这里，我们回顾了非编码RNA如何在人类细胞中的转录和表观遗传基因沉默的调节中发挥作用，通过回顾这些早期的研究和迄今为止获得的机制见解。我们还提供了一个哺乳动物的基因，已被证明是转录调控的非编码RNA的列表。最后，我们探讨了TGS如何作为未来治疗药物开发的基础。
It has been over a decade since the first observation that small non-coding RNAs can functionally modulate epigenetic states in human cells to achieve functional transcriptional gene silencing (TGS). TGS is mechanistically distinct from the RNA interference (RNAi) gene-silencing pathway. TGS can result in long-term stable epigenetic modifications to gene expression that can be passed on to daughter cells during cell division, whereas RNAi does not. Early studies of TGS have been largely overlooked, overshadowed by subsequent discoveries of small RNA-directed post-TGS and RNAi. A reappraisal of early work has been brought about by recent findings in human cells where endogenous long non-coding RNAs function to regulate the epigenome. There are distinct and common overlaps between the proteins involved in small and long non-coding RNA transcriptional regulatory mechanisms, suggesting that the early studies using small non-coding RNAs to modulate transcription were making use of a previously unrecognized endogenous mechanism of RNA-directed gene regulation. Here we review how non-coding RNA plays a role in regulation of transcription and epigenetic gene silencing in human cells by revisiting these earlier studies and the mechanistic insights gained to date. We also provide a list of mammalian genes that have been shown to be transcriptionally regulated by non-coding RNAs. Lastly, we explore how TGS may serve as the basis for development of future therapeutic agents.
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DOI：
10.1038/mtna.2013.33
发表时间：
2013-07-09
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1038/mtna.2015.31
发表时间：
2015-10-27
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Ahlenstiel C;Mendez C;Lim ST;Marks K;Turville S;Cooper DA;Kelleher AD;Suzuki K
通讯作者：
Suzuki K
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
BRENNER, S;MESELSON, M;JACOB, F
通讯作者：
JACOB, F