Features and mechanisms of long-lived Myotis somatic fibroblasts in response to DNA replication stress.

IF 4 1区 生物学 Q1 ZOOLOGY
Xiao-Yan Huang, Xiu-Yun Liu, Wei Wang, Gao-Jing Liu, You-Long Zhu, Xiao Wen, Kai-Qin Li, Bo Zhao
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Abstract

The DNA replication stress (RS) response is crucial for maintaining cellular homeostasis and promoting physiological longevity. However, the mechanisms by which long-lived species, such as bats, regulate RS to maintain genomic stability remain unclear. Also, recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability. In this study, somatic skin fibroblasts from the long-lived big-footed bat ( Myotis pilosus) were examined, with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells. Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences, including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway. These features emphasize a distinct homeostatic strategy in bat cells. Nuclear fragile X mental retardation-interacting protein 1 ( Nufip1), a ribosome-associated factor highly expressed in bat fibroblasts, was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like (Rps27l). These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats, highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.

长寿命肌炎体细胞成纤维细胞对DNA复制应激反应的特征和机制。
DNA复制应激反应对于维持细胞稳态和促进生理寿命至关重要。然而,蝙蝠等长寿物种调节RS以维持基因组稳定性的机制尚不清楚。此外,最近的研究揭示了核糖体相关因子在维持基因组稳定性中的非规范作用。在这项研究中,研究人员检测了长寿的大脚蝙蝠(Myotis pilosus)的体细胞皮肤成纤维细胞,结果表明,与小鼠细胞相比,蝙蝠细胞表现出更强的RS耐受性。RS条件下的比较转录组分析揭示了明显的物种特异性转录差异,包括蝙蝠细胞中核糖体生物发生基因的显著上调和P53信号通路的显著降低。这些特征强调了蝙蝠细胞中独特的稳态策略。核脆性X智力发育迟缓相互作用蛋白1 (Nufip1)是一种在蝙蝠成纤维细胞中高度表达的核糖体相关因子,通过与核糖体蛋白s27样(Rps27l)的关联,被确定为核糖体和P53信号的潜在整合者。这些发现为蝙蝠非典型RS反应提供了直接的细胞和分子证据,突出了对长寿物种的生物学特征和基因组维持机制的更深入了解。
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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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