MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
PLoS Genet. 2023 Oct 16;19(10):e1010985. doi: 10.1371/journal.pgen.1010985. eCollection 2023 Oct.
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.
UPF1-UPF2-UPF3 复合物协调的无意义介导的 mRNA 降解（NMD）是一种已被充分研究的真核细胞监视机制，它不仅能降解异常转录本以保护转录组的完整性，还能消除正常转录本以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控作用，该基因对于清除 H2O2 诱导的氧化应激至关重要。首先，失去 UPF 蛋白会显著减缓 cat-3 mRNA 的降解速度。其次，UPF 蛋白通过增强编码一个研究充分的转录因子和组蛋白乙酰转移酶的 cpc-1 和 ngf-1 mRNA 的降解来间接减弱 cat-3 基因的转录活性。进一步的研究表明，在氧化应激条件下，UPF 蛋白被降解，随后 CPC-1 和 NGF-1 的活性增加，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，UPF 复合物介导的 cat-3 基因的复杂调控网络。
