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Sensing of H2O2-induced oxidative stress by the UPF factor complex is crucial for activation of catalase-3 expression in Neurospora.
PLOS Genetics ( IF 4.5 ) Pub Date : 2023-10-16 , DOI: 10.1371/journal.pgen.1010985
Shuangjie Shen 1 , Chengcheng Zhang 1 , Yuanhao Meng 1 , Guofei Cui 1 , Ying Wang 1 , Xiao Liu 2, 3 , Qun He 1
Affiliation  

UPF-1-UPF-2-UPF-3 complex-orchestrated nonsense-mediated mRNA decay (NMD) is a well-characterized eukaryotic cellular surveillance mechanism that not only degrades aberrant transcripts to protect the integrity of the transcriptome but also eliminates normal transcripts to facilitate appropriate cellular responses to physiological and environmental changes. Here, we describe the multifaceted regulatory roles of the Neurospora crassa UPF complex in catalase-3 (cat-3) gene expression, which is essential for scavenging H2O2-induced oxidative stress. First, losing UPF proteins markedly slowed down the decay rate of cat-3 mRNA. Second, UPF proteins indirectly attenuated the transcriptional activity of cat-3 gene by boosting the decay of cpc-1 and ngf-1 mRNAs, which encode a well-studied transcription factor and a histone acetyltransferase, respectively. Further study showed that under oxidative stress condition, UPF proteins were degraded, followed by increased CPC-1 and NGF-1 activity, finally activating cat-3 expression to resist oxidative stress. Together, our data illustrate a sophisticated regulatory network of the cat-3 gene mediated by the UPF complex under physiological and H2O2-induced oxidative stress conditions.

中文翻译:

UPF 因子复合物对 H2O2 诱导的氧化应激的感知对于脉孢菌中过氧化氢酶 3 表达的激活至关重要。

UPF-1-UPF-2-UPF-3 复合体编排的无义介导的 mRNA 衰减 (NMD) 是一种充分表征的真核细胞监视机制,不仅可以降解异常转录本以保护转录组的完整性,还可以消除正常转录本以保护转录组的完整性。促进细胞对生理和环境变化的适当反应。在这里,我们描述了粗糙脉孢菌 UPF 复合物在过氧化氢酶 3 (cat-3) 基因表达中的多方面调节作用,这对于清除 H2O2 诱导的氧化应激至关重要。首先,失去 UPF 蛋白显着减缓了 cat-3 mRNA 的衰减速度。其次,UPF 蛋白通过促进 cpc-1 和 ngf-1 mRNA 的衰变间接减弱 cat-3 基因的转录活性,cpc-1 和 ngf-1 mRNA 分别编码经过充分研究的转录因子和组蛋白乙酰转移酶。进一步研究表明,在氧化应激条件下,UPF蛋白被降解,随后CPC-1和NGF-1活性增加,最终激活cat-3表达以抵抗氧化应激。总之,我们的数据说明了在生理和 H2O2 诱导的氧化应激条件下由 UPF 复合物介导的 cat-3 基因的复杂调控网络。
更新日期:2023-10-16
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