RNA Polymerase III, Ageing and Longevity.
RNA Polymerase III, Ageing and Longevity.
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DOI：
10.3389/fgene.2021.705122
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发表时间：
2021
影响因子：
3.7
通讯作者：
Tullet JMA
中科院分区：
文献类型：
--
作者：
Kulaberoglu Y;Malik Y;Borland G;Selman C;Alic N;Tullet JMA
真核细胞中的转录由三种RNA聚合酶进行。RNA聚合酶I合成大多数rRNA，而RNA聚合酶II转录所有mRNA和许多非编码RNA。三种聚合酶中最大的是RNA聚合酶III（Pol III），其转录多种短的非编码RNA，包括tRNA和5S rRNA，以及其他小RNA，如snRNA、snoRNA、西内斯、7SL RNA、Y RNA和U6 spilceosomal RNA。Pol III介导的转录是高度动态的，并且响应于细胞生长、细胞增殖和应激的变化而受到调节。Pol III产生的转录物参与多种细胞过程，包括翻译、基因组和转录组调控以及RNA加工，其中Pol III失调涉及包括脑白质营养不良、阿尔茨海默氏症、脆性X综合征和各种癌症的疾病。最近，Pol III被鉴定为作用于mTORC 1下游的生物体寿命的进化保守决定因素。Pol III抑制延长酵母、蠕虫和苍蝇的寿命，并且在蠕虫和苍蝇中分别从肠和肠干细胞起作用以实现这一点。有趣的是，通过损害其主阻遏物Maf 1实现的Pol III激活也已被证明可以促进包括小鼠在内的模型生物的寿命。在这篇综述中，我们介绍了Pol III转录装置和审查目前的理解RNA Pol III的作用，在不同的模式生物的老化和寿命。然后，我们讨论了Pol III作为改善人类年龄相关健康的治疗靶点的潜力。
Transcription in eukaryotic cells is performed by three RNA polymerases. RNA polymerase I synthesises most rRNAs, whilst RNA polymerase II transcribes all mRNAs and many non-coding RNAs. The largest of the three polymerases is RNA polymerase III (Pol III) which transcribes a variety of short non-coding RNAs including tRNAs and the 5S rRNA, in addition to other small RNAs such as snRNAs, snoRNAs, SINEs, 7SL RNA, Y RNA, and U6 spilceosomal RNA. Pol III-mediated transcription is highly dynamic and regulated in response to changes in cell growth, cell proliferation and stress. Pol III-generated transcripts are involved in a wide variety of cellular processes, including translation, genome and transcriptome regulation and RNA processing, with Pol III dys-regulation implicated in diseases including leukodystrophy, Alzheimer’s, Fragile X-syndrome and various cancers. More recently, Pol III was identified as an evolutionarily conserved determinant of organismal lifespan acting downstream of mTORC1. Pol III inhibition extends lifespan in yeast, worms and flies, and in worms and flies acts from the intestine and intestinal stem cells respectively to achieve this. Intriguingly, Pol III activation achieved through impairment of its master repressor, Maf1, has also been shown to promote longevity in model organisms, including mice. In this review we introduce the Pol III transcription apparatus and review the current understanding of RNA Pol III’s role in ageing and lifespan in different model organisms. We then discuss the potential of Pol III as a therapeutic target to improve age-related health in humans.
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影响因子：
64.5
作者：
Gouge J;Satia K;Guthertz N;Widya M;Thompson AJ;Cousin P;Dergai O;Hernandez N;Vannini A
通讯作者：
Vannini A
影响因子：
29
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通讯作者：
Partridge L
影响因子：
5.4
作者：
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通讯作者：
White, Robert J.
影响因子：
13.8
作者：
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通讯作者：
Maraia RJ
影响因子：
5.3
作者：
Ciesla, Malgorzata;Towpik, Joanna;Boguta, Magdalena
通讯作者：
Boguta, Magdalena