Yonsei Proteome Research Center, Yonsei University, Seoul 03722, Korea.
Int J Mol Sci. 2020 Mar 29;21(7):2366. doi: 10.3390/ijms21072366.
Under stressful conditions, the early larvae of enter dauer diapause, a non-aging period, driven by the seemingly opposite influence of ascaroside pheromones (ASCRs) and steroid hormone dafachronic acids (DAs). However, the molecular basis of how these small molecules engage in competitive crosstalk in coordination with insulin/IGF-1 signaling (IIS) remains elusive. Here we report a novel transcriptional regulatory pathway that seems to operate between the ASCR and DA biosynthesis under (AL) feeding conditions or bacterial deprivation (BD). Although expression of the ASCR and DA biosynthetic genes reciprocally inhibit each other, ironically and interestingly, such dietary cue-mediated modulation requires the presence of the competitors. Under BD, induction of ASCR biosynthetic gene expression required DA, while ASCR suppresses the expression of the DA biosynthetic gene . The negative regulation of DA by ASCR was IIS-dependent, whereas regulation appeared to be independent of IIS. These observations suggest that the presence of ASCR determines the IIS-dependency of DA gene expression regardless of dietary conditions. Thus, our work defines a molecular basis for a novel reciprocal gene regulation of pheromones and hormones to cope with stressful conditions during development and aging.
在应激条件下， enter dauer 幼虫进入非衰老期 dauer 休眠，这是由似乎相反的阿莎菌素信息素 (ASCRs) 和类固醇激素 dafachronic 酸 (DAs) 的影响驱动的。然而，这些小分子如何与胰岛素/IGF-1 信号 (IIS) 进行竞争性串扰的分子基础仍然难以捉摸。在这里，我们报告了一种似乎在 ASCR 和 DA 生物合成之间起作用的新型转录调控途径，这种途径似乎在 (AL) 喂养条件或细菌剥夺 (BD) 下发挥作用。尽管 ASCR 和 DA 生物合成基因的表达相互抑制，但具有讽刺意味的是，这种饮食线索介导的调节需要存在竞争物。在 BD 下，ASCR 生物合成基因表达的诱导需要 DA，而 ASCR 抑制了 DA 生物合成基因的表达。ASCR 对 DA 的负调控依赖于 IIS，而 调控似乎独立于 IIS。这些观察结果表明，ASCR 的存在决定了 IIS 对 DA 基因表达的依赖性，而不论饮食条件如何。因此，我们的工作为应对发育和衰老过程中的应激条件，确定了一种新型信息素和激素相互调节的分子基础。
