草莓notch 1通过调控yeat4的表达来保护神经元基因组。

IF 7 2区 生物学 Q1 CELL BIOLOGY
Dai Ihara, Ayano Narumoto, Yukie Kande, Tomoki Hayashi, Yasuaki Ikuno, Manabu Shirai, Masaki Wakabayashi, Ryo Nitta, Hayato Naka-Kaneda, Yu Katsuyama
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引用次数: 0

摘要

神经元受到各种各样的压力,包括高代谢需求、生理活动和转录调节,它们的基因组DNA是脆弱的。神经元基因组的稳定对正常的脑生理功能至关重要。准确的基因组DNA修复失败可导致神经功能异常或细胞死亡。基因组不稳定性与神经发育和神经退行性疾病的风险增加有关。然而,神经元基因组稳定性的分子机制仍然知之甚少。草莓缺口同源物1 (SBNO1)的突变被认为与这些疾病有关。在这里,我们研究了sno1敲除(KO)小鼠皮层中观察到的组织学异常的分子机制。综合基因表达分析显示,Sbno1 KO影响细胞存活相关基因的表达,这与Sbno1 KO皮质细胞凋亡增加一致。在Sbno1 KO中下调的基因中,我们重点关注了yeat4。过表达Yeats4挽救了由sno1缺失引起的基因组DNA损伤的积累和细胞死亡。这些发现表明,sno1至少在一定程度上通过调节yeat4的表达,在保护神经元基因组方面起着至关重要的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Strawberry notch 1 safeguards neuronal genome via regulation of Yeats4 expression.

Neurons are subjected to various stresses, including high metabolic demand, physiological activity, and transcriptional regulation, to which their genomic DNA are vulnerable. Genome stability of neurons is essential for proper physiological brain function. Failure in accurate genomic DNA repair can result in abnormal neuronal functions or cell death. Genomic instability has been implicated in increased risks of neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying neuronal genome stability remain poorly understood. Mutations in the Strawberry Notch Homolog 1 (SBNO1) have been suggested to contribute to these disorders. Here, we investigated the molecular mechanisms underlying histological abnormalities observed in the cortex of Sbno1 knockout (KO) mice. Comprehensive gene expression analysis revealed that Sbno1 KO affects the expression of genes related to cell survival, consistent with the increased apoptosis observed in Sbno1 KO cortices. Among the genes downregulated in Sbno1 KO, we focused on Yeats4. Overexpression of Yeats4 rescued the accumulation of genomic DNA damage and cell death caused by Sbno1 deletion. These findings suggest that Sbno1 is critical in safeguarding the neuronal genome, at least in part, via regulating Yeats4 expression.

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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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