The Rodent-Specific MicroRNA Cluster within the Sfmbt2 Gene Is Imprinted and Essential for Placental Development
The Rodent-Specific MicroRNA Cluster within the Sfmbt2 Gene Is Imprinted and Essential for Placental Development
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DOI：
10.1016/j.celrep.2017.04.018
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发表时间：
2017-05-02
期刊：
影响因子：
8.8
通讯作者：
Ogura, Atsuo
中科院分区：
文献类型：
--
作者：
Inoue, Kimiko;Hirose, Michiko;Ogura, Atsuo
microRNA（miRNAs）是一类通过转录后抑制基因表达参与生理和发育过程的非编码小分子RNA。小鼠中最大的miRNA簇之一位于Sfmbt2基因的内含子10，包含72个miRNA前体序列。在这项研究中，我们产生了缺乏整个Sfmbt2 miRNA簇的小鼠，以阐明其在发育过程中的功能。与宿主Sfmbt2基因一样，Sfmbt2 miRNA主要由胎盘中的父系等位基因表达。父亲等位基因的丢失导致胎盘发育严重受损，尤其是海绵滋养层，并经常导致胎儿死亡或缺陷。预测的miRNAs靶序列和基因表达分析确定了至少9个推定的靶基因，其功能为肿瘤抑制因子或凋亡诱导因子。我们的研究为胎盘miRNAs在滋养层细胞增殖和胎儿发育中不可或缺的作用提供了实验证据。
MicroRNAs (miRNAs) represent small noncoding RNAs that are involved in physiological and developmental processes by posttranscriptionally inhibiting gene expression. One of the largest miRNA clusters in mice is located in intron 10 of the Sfmbt2 gene, containing 72 miRNA precursor sequences. In this study, we generated mice lacking the entire Sfmbt2 miRNA cluster to elucidate its functions during development. The Sfmbt2 miRNAs were expressed predominantly from the paternal allele in the placenta, as is the host Sfmbt2 gene. Loss of the paternal allele resulted in severely impaired development of the placenta, especially the spongiotrophoblast layer, and frequent lethality or defects of fetuses. The predicted target sequences of the miRNAs and gene expression analysis defined at least nine putative target genes, which function as tumor suppressors or apoptosis inducers. Our study has provided experimental evidence for the indispensable roles of placental miRNAs in trophoblast proliferation and thus fetal development.