Ow Maria C, Nishiguchi Mailyn A, Dar Abdul Rouf, Butcher Rebecca A, Hall Sarah E
Biology Department, Syracuse University, Syracuse, NY, United States.
Department of Chemistry, University of Florida, Gainesville, FL, United States.
Front Mol Biosci. 2024 Jul 11;11:1396587. doi: 10.3389/fmolb.2024.1396587. eCollection 2024.
Environmental conditions experienced early in the life of an animal can result in gene expression changes later in its life history. We have previously shown that animals that experienced the developmentally arrested and stress resistant dauer stage (postdauers) retain a cellular memory of early-life stress that manifests during adulthood as genome-wide changes in gene expression, chromatin states, and altered life history traits. One consequence of developmental reprogramming in postdauer adults is the downregulation of TRPV channel gene expression in the ADL chemosensory neurons resulting in reduced avoidance to a pheromone component, ascr#3. This altered response to ascr#3 requires the principal effector of the somatic nuclear RNAi pathway, the Argonaute (AGO) NRDE-3. To investigate the role of the somatic nuclear RNAi pathway in regulating the developmental reprogramming of ADL due to early-life stress, we profiled the mRNA transcriptome of control and postdauer ADL in wild-type and mutant adults. We found 711 differentially expressed (DE) genes between control and postdauer ADL neurons, 90% of which are dependent upon NRDE-3. Additionally, we identified a conserved sequence that is enriched in the upstream regulatory sequences of the NRDE-3-dependent differentially expressed genes. Surprisingly, 214 of the ADL DE genes are considered "germline-expressed", including 21 genes encoding the Major Sperm Proteins and two genes encoding the sperm-specific PP1 phosphatases, GSP-3 and GSP-4. Loss of function mutations in resulted in both aberrant avoidance and attraction behaviors. We also show that an AGO pseudogene, Y49F6A.1 (), is expressed in ADL and is required for ascr#3 avoidance. Overall, our results suggest that small RNAs and reproductive genes program the ADL mRNA transcriptome during their developmental history and highlight a nexus between neuronal and reproductive networks in calibrating animal neuroplasticity.
动物生命早期所经历的环境条件会导致其生命后期基因表达发生变化。我们之前已经表明，经历了发育停滞且具有抗应激能力的 dauer 阶段（滞育后阶段）的动物会保留早期生活应激的细胞记忆，这种记忆在成年期表现为全基因组范围的基因表达、染色质状态变化以及生活史特征改变。滞育后成年动物发育重编程的一个后果是，ADL 化学感受神经元中 TRPV 通道基因表达下调，导致对信息素成分 ascr#3 的回避减少。这种对 ascr#3 的反应改变需要体细胞细胞核 RNAi 途径的主要效应物 Argonaute（AGO）NRDE - 3。为了研究体细胞细胞核 RNAi 途径在调节因早期生活应激导致的 ADL 发育重编程中的作用，我们分析了野生型和突变型成年动物中对照和滞育后 ADL 的 mRNA 转录组。我们发现对照和滞育后 ADL 神经元之间有 711 个差异表达（DE）基因，其中 90%依赖于 NRDE - 3。此外，我们鉴定出一个保守序列，该序列在 NRDE - 3 依赖的差异表达基因的上游调控序列中富集。令人惊讶的是，ADL 的 DE 基因中有 214 个被认为是“种系表达的”，包括 21 个编码主要精子蛋白的基因以及两个编码精子特异性 PP1 磷酸酶 GSP - 3 和 GSP - 4 的基因。相关功能缺失突变导致异常的回避和吸引行为。我们还表明，一个 AGO 假基因 Y49F6A.1（）在 ADL 中表达，并且是回避 ascr#3 所必需的。总体而言，我们的结果表明，小 RNA 和生殖基因在其发育过程中对 ADL 的 mRNA 转录组进行编程，并突出了神经元和生殖网络在校准动物神经可塑性方面的联系。
