MiR-290 family maintains developmental potential by targeting p21 in mouse pre-implantation embryos.
MiR-290 family maintains developmental potential by targeting p21 in mouse pre-implantation embryos.
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MiR-290 家族通过靶向小鼠植入前胚胎中的 p21 来维持发育潜力。
DOI：
10.1093/biolre/ioab227
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发表时间：
2021
影响因子：
3.6
通讯作者：
Yu Haiquan
中科院分区：
文献类型：
--
作者：
Li Xiangnan;Liu Yueshi;Mu Qier;Tian Junliang;Yu Haiquan
miR-290 家族是小鼠特异性的 microRNA 簇，通过增加 OCT3/4 和 C-MYC 的表达来维持小鼠胚胎干细胞 (ESC) 的多能性。然而，其在小鼠植入前胚胎中的功能仍不清楚，特别是在合子基因组激活（ZGA）期间。在这项研究中，miR-290家族的表达从两细胞胚胎阶段到囊胚阶段均增加。抑制miR-294-3p/5p不影响ZGA启动或胚胎发育，而pri-miR-290敲低则降低ZGA基因表达并减慢胚胎发育。此外，来自pri-miR-290敲低囊胚的ESCs的多能性降低。为了阐明作用机制，从三个数据库中筛选了33个候选miR-294-3p靶基因，miR-294-3p直接靶向Cdkn1a(p21) mRNA的3'非翻译区。与 topri-miR-290 敲低类似，P21 过表达阻碍胚胎发育，而 P21 和 pri-miR-290 同时过表达部分挽救胚胎发育。结果表明，miR-290家族通过靶向p21参与促进ZGA过程并维持胚胎发育潜能。
The miR-290 family is a mouse-specific microRNA cluster, which maintains mouse embryonic stem cells (ESCs) pluripotency by increasing OCT3/4 and C-MYC expression. However, its functions in mouse preimplantation embryos remain unclear, especially during zygotic genome activation (ZGA). In this study, miR-290 family expression increased from the two-cell embryo stage through the blastocyst stage. Inhibition ofmiR-294-3p/5pdid not affect ZGA initiation or embryo development, whereaspri-miR-290knockdown decreased ZGA gene expression and slowed embryonic development. In addition, pluripotency decreased in ESCs derived frompri-miR-290knockdown blastocysts. To clarify the mechanism of action, 33 candidatemiR-294-3ptarget genes were screened from three databases, andmiR-294-3pdirectly targeted the 3′-untranslated region ofCdkn1a(p21) mRNA. Similar topri-miR-290knockdown, P21 overexpression impeded embryonic development, whereas simultaneous overexpression of P21 andpri-miR-290partially rescued embryonic development. The results indicate that the miR-290 family participates in promoting ZGA process and maintaining developmental potency in embryos by targetingp21.