New insights into nucleolar structure and function.

New insights into nucleolar structure and function.
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DOI:
10.12703/p7-48
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发表时间:
2015
期刊:
F1000prime reports
影响因子:
--
通讯作者:
Trinkle-Mulcahy L
Trinkle-Mulcahy L
中科院分区:
其他
文献类型:
--
作者:
Lam YW;Trinkle-Mulcahy L

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核仁是所有真核生物中发现的非膜结合的核细胞器。它是典型的“RNA种子”核体,围绕特定的染色体特征形成,称为核仁组织区,包含核糖体DNA阵列。组装是由RNA聚合酶I介导的转录激活触发的,并在哺乳动物细胞中以细胞周期依赖性方式进行调节。虽然核仁最为人所知的是它在协调核糖体生物发生中的作用,但生物化学和蛋白质组学分析揭示了比以前认识到的更广泛的功能复杂性,包括细胞周期调节,DNA损伤传感和修复,前mRNA加工,端粒代谢,非编码RNA的加工以及协调细胞对各种应激的反应。尽管取得了这些进展,但仍有许多关于在该细胞器内发生或涉及该细胞器的全方位生物过程以及如何调节其组装/拆卸和功能重组以响应各种刺激的信息。在这里,我们回顾了最近的研究,提供了这些基本问题的主要见解的影响,我们强调的治疗潜力,针对核仁途径。
The nucleolus is a non-membrane-bound nuclear organelle found in all eukaryotes. It is the quintessential ‘RNA-seeded’ nuclear body, forming around specific chromosomal features called nucleolar organizing regions that contain arrays of ribosomal DNA. Assembly is triggered by activation of RNA polymerase I-mediated transcription and regulated in mammalian cells in a cell cycle-dependent manner. Although the nucleolus is best known for its role in coordinating ribosome biogenesis, biochemical and proteomic analyses have revealed a much wider functional complexity than previously appreciated, including roles in cell cycle regulation, DNA damage sensing and repair, pre-mRNA processing, telomere metabolism, processing of non-coding RNAs, and coordination of the cellular response to various stresses. Despite these advances, much remains to be learned about the full range of biological processes that occur within, or involve, this organelle and how its assembly/disassembly and functional reorganization in response to various stimuli are regulated. Here, we review the impact of recent studies that provide major insights into these fundamental questions, and we highlight the therapeutic potential of targeting nucleolar pathways.