Brunquell Jessica, Snyder Alana, Cheng Feng, Westerheide Sandy D
Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, Florida, United States of America.
Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America.
PLoS One. 2017 Aug 24;12(8):e0183445. doi: 10.1371/journal.pone.0183445. eCollection 2017.
The ability of an organism to sense and adapt to environmental stressors is essential for proteome maintenance and survival. The highly conserved heat shock response is a survival mechanism employed by all organisms, including the nematode Caenorhabditis elegans, upon exposure to environmental extremes. Transcriptional control of the metazoan heat shock response is mediated by the heat shock transcription factor HSF-1. In addition to regulating global stress-responsive genes to promote stress-resistance and survival, HSF-1 has recently been shown to regulate stress-independent functions in controlling development, metabolism, and longevity. However, the indirect role of HSF-1 in coordinating stress-dependent and -independent processes through post-transcriptional regulation is largely unknown. MicroRNAs (miRNAs) have emerged as a class of post-transcriptional regulators that control gene expression through translational repression or mRNA degradation. To determine the role of HSF-1 in regulating miRNA expression, we have performed high-throughput small RNA-sequencing in C. elegans grown in the presence and absence of hsf-1 RNAi followed by treatment with or without heat shock. This has allowed us to uncover the miRNAs regulated by HSF-1 via heat-dependent and -independent mechanisms. Integrated miRNA/mRNA target-prediction analyses suggest HSF-1 as a post-transcriptional regulator of development, metabolism, and longevity through regulating miRNA expression. This provides new insight into the possible mechanism by which HSF-1 controls these processes. We have also uncovered oxidative stress response factors and insulin-like signaling factors as a common link between processes affected by HSF-1-regulated miRNAs in stress-dependent and -independent mechanisms, respectively. This may provide a role for miRNAs in regulating cross-talk between various stress responses. Our work therefore uncovers an interesting potential role for HSF-1 in post-transcriptionally controlling gene expression in C. elegans, and suggests a mechanism for cross-talk between stress responses.
生物体感知并适应环境应激源的能力对于蛋白质组维持和生存至关重要。高度保守的热休克反应是包括线虫秀丽隐杆线虫在内的所有生物体在暴露于极端环境时所采用的一种生存机制。后生动物热休克反应的转录调控由热休克转录因子HSF-1介导。除了调节全局应激反应基因以促进应激抗性和生存外，最近还发现HSF-1在控制发育、代谢和寿命方面调节与应激无关的功能。然而，HSF-1通过转录后调控在协调应激依赖性和非依赖性过程中的间接作用在很大程度上尚不清楚。微小RNA（miRNA）已成为一类转录后调节因子，通过翻译抑制或mRNA降解来控制基因表达。为了确定HSF-1在调节miRNA表达中的作用，我们在存在和不存在hsf-1 RNA干扰的情况下培养秀丽隐杆线虫，然后进行或不进行热休克处理，之后进行了高通量小RNA测序。这使我们能够揭示HSF-1通过热依赖性和非依赖性机制调节的miRNA。综合的miRNA/mRNA靶标预测分析表明，HSF-1通过调节miRNA表达作为发育、代谢和寿命的转录后调节因子。这为HSF-1控制这些过程的可能机制提供了新的见解。我们还分别发现氧化应激反应因子和胰岛素样信号因子是受HSF-1调节的miRNA在应激依赖性和非依赖性机制中影响的过程之间的共同联系。这可能为miRNA在调节各种应激反应之间的相互作用中发挥作用。因此，我们的工作揭示了HSF-1在转录后控制秀丽隐杆线虫基因表达方面一个有趣的潜在作用，并提出了应激反应之间相互作用的机制。
