The small RNA landscape is stable with age and resistant to loss of dFOXO signaling in Drosophila.
The small RNA landscape is stable with age and resistant to loss of dFOXO signaling in Drosophila.
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DOI：
10.1371/journal.pone.0273590
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
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衰老可以被定义为导致细胞和有机体功能下降的生理稳态的逐渐丧失。近年来，已经清楚的是，小RNA途径在衰老和衰老相关表型中发挥作用。小RNA通路调节许多重要的过程，包括发育，细胞生理学和先天免疫。该途径非法的转录后基因调控的形式，依赖于小RNA结合的RNA诱导的沉默复合物（RISC）的蛋白质成分，抑制互补RNA的表达。在果蝇中，Argonaute 1（Ago1）是microRNA（miRNA）沉默的核心RISC组分，而Argonaute 2（Ago2）是小干扰RNA（siRNA）沉默的核心RISC组分。Ago1和Ago2的表达受应激反应转录因子Forkhead box O（dFOXO）的调节，增加siRNA沉默效率。dFOXO在多种应激反应中发挥作用，并调节对长寿重要的途径。在这里，我们使用下一代测序方法来确定衰老对雄性和雌性果蝇中小RNA丰度和RISC加载的影响。此外，我们还研究了dFOXO的损失对这些过程的影响。我们发现，大多数小RNA的相对丰度不随年龄而变化。此外，在正常生长条件下，dFOXO的丢失对小RNA景观几乎没有影响。然而，我们观察到年龄影响少量miRNA加载到RISC中。
Aging can be defined as the progressive loss of physiological homeostasis that leads to a decline in cellular and organismal function. In recent years, it has become clear that small RNA pathways play a role in aging and aging related phenotypes. Small RNA pathways regulate many important processes including development, cellular physiology, and innate immunity. The pathways illicit a form of posttranscriptional gene regulation that relies on small RNAs bound by the protein components of the RNA-induced silencing complexes (RISCs), which inhibit the expression of complementary RNAs. In Drosophila melanogaster, Argonaute 1 (Ago1) is the core RISC component in microRNA (miRNA) silencing, while Argonaute 2 (Ago2) is the core RISC component in small interfering RNA (siRNA) silencing. The expression of Ago1 and Ago2 is regulated by stress response transcription factor Forkhead box O (dFOXO) increasing siRNA silencing efficiency. dFOXO plays a role in multiple stress responses and regulates pathways important for longevity. Here we use a next-generation sequencing approach to determine the effects of aging on small RNA abundance and RISC loading in male and female Drosophila. In addition, we examine the impact of the loss of dFOXO on these processes. We find that the relative abundance of the majority of small RNAs does not change with age. Additionally, under normal growth conditions, the loss of dFOXO has little effect on the small RNA landscape. However, we observed that age affects loading into RISC for a small number of miRNAs.
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