Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia , Charlottesville, VA, USA.
Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia , Charlottesville, VA, USA.
RNA Biol. 2020 Aug;17(8):1183-1195. doi: 10.1080/15476286.2020.1721047. Epub 2020 Jan 31.
tRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the foetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5' tRNA halves from tRNA, tRNA, tRNA and tRNA are abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 h after MIA and are suppressed thereafter. A group of 5' tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.
tRNA 衍生的小片段 (tRFs) 和 tRNA 片段在不同的生物学途径中具有新兴的功能，例如调节基因表达、蛋白质翻译、逆转录转座子活性、跨代表观遗传变化和对环境应激的反应。然而，在妊娠期间母胎界面中的像 tRFs 和 microRNAs 这样的小 RNA 尚未得到广泛研究。在这里，我们研究了代表母体与胎儿交流界面的小鼠胎盘/蜕膜中的小 RNA 组成，以确定在胎儿发育过程中和对母体免疫激活 (MIA) 时是否存在 tRFs 和 microRNAs 的特定差异。像 microRNAs 一样，全局 tRF 表达模式可以区分胎盘/蜕膜、胎脑和胎肝之间的组织类型。特别是，tRNA、tRNA、tRNA 和 tRNA 的 5' tRNA 片段在正常小鼠胎盘/蜕膜中大量表达。此外，母胎界面中的 tRF 和 microRNA 水平在胚胎发育过程中动态变化。为了观察应激是否改变母胎界面的非编码 RNA 表达，我们用病毒感染模拟物处理怀孕的小鼠，该模拟物已被证明会促进后代自闭症相关表型。在 MIA 后 3-6 小时观察到特定 tRFs 和 microRNAs 水平的急性变化，此后受到抑制。一组 5' tRNA 片段被 MIA 下调，而一组 18 个核苷酸的 tRF-3a 被上调。总之，tRFs 表现出组织特异性、发育变化和对环境应激的急性反应，这使得它们有可能在胎儿对 MIA 的反应中发挥作用。
