Li Xiangnan, Liu Yueshi, Mu Qier, Tian Junliang, Yu Haiquan
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (RRBGL), Inner Mongolia University, Hohhot, China.
Biol Reprod. 2022 Mar 19;106(3):425-440. doi: 10.1093/biolre/ioab227.
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 of miR-294-3p/5p did not affect ZGA initiation or embryo development, whereas pri-miR-290 knockdown decreased ZGA gene expression and slowed embryonic development. In addition, pluripotency decreased in ESCs derived from pri-miR-290 knockdown blastocysts. To clarify the mechanism of action, 33 candidate miR-294-3p target genes were screened from three databases, and miR-294-3p directly targeted the 3'-untranslated region of Cdkn1a (p21) mRNA. Similar to pri-miR-290 knockdown, P21 overexpression impeded embryonic development, whereas simultaneous overexpression of P21 and pri-miR-290 partially rescued embryonic development. The results indicate that the miR-290 family participates in promoting ZGA process and maintaining developmental potency in embryos by targeting p21.
miR-290家族是小鼠特有的微小RNA簇，它通过增加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，尤其是在合子基因组激活（ZGA）过程中。在本研究中，miR-290家族的表达从二细胞胚胎阶段到囊胚阶段逐渐增加。抑制miR-294-3p/5p并不影响ZGA的起始或胚胎发育，而敲低pri-miR-290则会降低ZGA基因的表达并减缓胚胎发育。此外，从敲低pri-miR-290的囊胚中获得的ESC的多能性降低。为了阐明其作用机制，从三个数据库中筛选出33个候选miR-294-3p靶基因，并且miR-294-3p直接靶向Cdkn1a（p21）mRNA的3'-非翻译区。与敲低pri-miR-290类似，过表达P21会阻碍胚胎发育，而同时过表达P21和pri-miR-290则部分挽救胚胎发育。结果表明，miR-290家族通过靶向p21参与促进ZGA进程并维持胚胎的发育潜能。
