Wisconsin Blood Cancer Research Institute, Department of Cell and Regenerative Biology, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, 4009 WIMR, Madison, WI 53705, USA.
Nucleic Acids Res. 2020 Dec 2;48(21):11913-11928. doi: 10.1093/nar/gkaa883.
Given the complexity of intracellular RNA ensembles and vast phenotypic remodeling intrinsic to cellular differentiation, it is instructive to consider the role of RNA regulatory machinery in controlling differentiation. Dynamic post-transcriptional regulation of protein-coding and non-coding transcripts is vital for establishing and maintaining proteomes that enable or oppose differentiation. By contrast to extensively studied transcriptional mechanisms governing differentiation, many questions remain unanswered regarding the involvement of post-transcriptional mechanisms. Through its catalytic activity to selectively process or degrade RNAs, the RNA exosome complex dictates the levels of RNAs comprising multiple RNA classes, thereby regulating chromatin structure, gene expression and differentiation. Although the RNA exosome would be expected to control diverse biological processes, studies to elucidate its biological functions and how it integrates into, or functions in parallel with, cell type-specific transcriptional mechanisms are in their infancy. Mechanistic analyses have demonstrated that the RNA exosome confers expression of a differentiation regulatory receptor tyrosine kinase, downregulates the telomerase RNA component TERC, confers genomic stability and promotes DNA repair, which have considerable physiological and pathological implications. In this review, we address how a broadly operational RNA regulatory complex interfaces with cell type-specific machinery to control cellular differentiation.
鉴于细胞内 RNA 集合的复杂性和细胞分化所固有的巨大表型重塑，考虑 RNA 调控机制在控制分化中的作用是有益的。对蛋白编码和非编码转录物的动态转录后调控对于建立和维持使分化能够或反对的蛋白质组至关重要。与广泛研究的转录机制不同，关于转录后机制的参与仍有许多问题尚未得到解答。RNA 外切体复合物通过其对 RNA 的选择性加工或降解的催化活性，决定了多种 RNA 类别组成的 RNA 的水平，从而调节染色质结构、基因表达和分化。尽管 RNA 外切体有望控制多种生物过程，但阐明其生物学功能以及它如何与细胞类型特异性转录机制整合或平行发挥作用的研究仍处于起步阶段。机制分析表明，RNA 外切体赋予分化调节受体酪氨酸激酶的表达，下调端粒酶 RNA 成分 TERC，赋予基因组稳定性并促进 DNA 修复，这具有相当大的生理和病理意义。在这篇综述中，我们探讨了广泛作用的 RNA 调控复合物如何与细胞类型特异性机制相互作用以控制细胞分化。
