MicroRNA expression is altered in lateral septum across reproductive stages.
MicroRNA expression is altered in lateral septum across reproductive stages.
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DOI：
10.1016/j.neuroscience.2015.11.019
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发表时间：
2016-01-15
期刊：
影响因子：
3.3
通讯作者：
Gammie SC
中科院分区：
文献类型：
--
作者：
Saul MC;Zhao C;Driessen TM;Eisinger BE;Gammie SC
MicroRNA (miRNA) 抑制 RNA 靶标，可能导致产后 CNS 基因表达变化，尽管这一点从未经过测试。在本研究中，我们使用 RNA 测序直接评估了雌性小鼠侧隔膜 (LS) 繁殖过程中的 miRNA 水平。我们发现，在其他三个阶段，即怀孕、产后第 1 天和产后第 8 天，miRNA 远离处女阶段的可靠且稳健的变化。对于在多个组中与原始条件显着不同的给定 miRNA，变化的方向始终是相同的。总体而言，我们鉴定了 32 个上调的 miRNA 和 25 个下调的 miRNA，它们与原始状态始终不同。 miR-433-3 和 miR-7b 发生“臂切换”。出乎意料的是，三分之一上调的 miRNA（相对于原始 miRNA）高度定位于 12 号染色体的 12qF1 区域，其中包括与干细胞和神经元分化有关的 Dlk1-Dio3 基因簇。超过 1500 个基因被多个上调的 miRNA 靶向，其中约 100 个基因被 5 个或更多 miRNA 靶向。超过 1000 个基因被多个下调的 miRNA 靶向，其中约 50 个基因被 5 个或更多 miRNA 靶向。一半的靶基因受到上调和下调的 miRNA 的调节，表明稳态调节。转录调控是与上调或下调 miRNA 相关的基因最丰富的途径。其他丰富的途径包括蛋白激酶活性（例如 MAP 激酶）、中枢神经系统发育、轴突引导、神经营养素信号传导、神经元发育/分化和神经发生。正如预期的那样，先前发表的产后 LS 基因表达变化是 LS miRNA 靶标的富集。令人惊讶的是，来自其他区域的产后基因表达变化也针对 LS miRNA 靶标而丰富，这表明一组核心 miRNA 可能在生殖过程中跨 CNS 发挥作用。我们一起直接检查 miRNA，发现产后大脑发生显着变化。
MicroRNAs (miRNAs) inhibit RNA targets and may contribute to postpartum CNS gene expression changes, although this has never been tested. In the present study, we directly evaluated miRNA levels using RNA sequencing during reproduction in female mice in lateral septum (LS). We found the reliable and robust changes of miRNAs away from the virgin stage at the three other stages, namely pregnant, day 1 postpartum, and day 8 postpartum. For a given miRNA that was significantly different from the virgin condition in more than one group, the direction of change was always the same. Overall, we identified 32 upregulated miRNAs and 25 downregulated miRNAs that were consistently different from the virgin state. ‘Arm switching’ occurs for miR-433-3 and miR-7b. Unexpectedly, a third of upregulated miRNAs (relative to virgin) were highly localized within the 12qF1 region of chromosome 12 that includes the Dlk1-Dio3 gene cluster implicated in stem cell and neuronal differentiation. Over 1500 genes were targeted by multiple upregulated miRNAs with about 100 genes targeted by 5 or more miRNAs. Over 1000 genes were targeted by multiple downregulated miRNAs with about 50 genes targeted by 5 or more miRNAs. Half of the target genes were regulated by up and downregulated miRNAs, indicating homeostatic regulation. Transcriptional regulation was the most enriched pathway for genes linked to up or down regulated miRNAs. Other enriched pathways included protein kinase activity (e.g., MAP kinase), CNS development, axon guidance, neurotrophin signaling, neuron development/differentiation, and neurogenesis. Previously published postpartum LS gene expression changes were enrichment for LS miRNA targets, as expected. Surprisingly, postpartum gene expression changes from other regions were also enriched against LS miRNA targets, suggesting a core group of miRNAs may act across the CNS during reproduction. Together, we directly examine miRNAs and find significant alterations in the postpartum brain.