RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease.

Hani S Zaher, Nima Mosammaparast
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Abstract

All cells are exposed to chemicals that can damage their nucleic acids. Cells must protect these polymers because they code for key factors or complexes essential for life. Much of the work on nucleic acid damage has naturally focused on DNA, partly due to the connection between mutagenesis and human disease, especially cancer. Recent work has shed light on the importance of RNA damage, which triggers a host of conserved RNA quality control mechanisms. Because many RNA species are transient, and because of their ability to be retranscribed, RNA damage has largely been ignored. Yet, because of the connection between damaged RNA and DNA during transcription, and the association between essential complexes that process or decode RNAs, notably spliceosomes and ribosomes, the appropriate handling of damaged RNAs is critical for maintaining cellular homeostasis. This notion is bolstered by disease states, including neurodevelopmental and neurodegenerative diseases, that may arise upon loss or misregulation of RNA quality control mechanisms.

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细胞稳态、基因组稳定性和疾病中的 RNA 损伤反应
所有细胞都会接触到可能损害其核酸的化学物质。细胞必须保护这些聚合物,因为它们编码着生命所必需的关键因子或复合物。有关核酸损伤的大部分工作自然都集中在 DNA 上,部分原因是突变与人类疾病(尤其是癌症)之间存在联系。最近的工作揭示了 RNA 损伤的重要性,它触发了一系列保守的 RNA 质量控制机制。由于许多 RNA 物种都是瞬时的,而且它们能够被重新转录,因此 RNA 损伤在很大程度上被忽视了。然而,由于转录过程中受损 RNA 与 DNA 之间的联系,以及处理或解码 RNA 的重要复合体(特别是剪接体和核糖体)之间的关联,适当处理受损 RNA 对于维持细胞平衡至关重要。包括神经发育性疾病和神经退行性疾病在内的疾病状态,可能会因 RNA 质量控制机制的缺失或失调而产生,这进一步证实了这一观点。
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来源期刊
CiteScore
62.60
自引率
0.00%
发文量
40
期刊介绍: The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.
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