4.5 Article

MiR-290 family maintains developmental potential by targeting p21 in mouse preimplantation embryos

Journal

BIOLOGY OF REPRODUCTION
Volume 106, Issue 3, Pages 425-440

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioab227

Keywords

MiRNAs; mouse embryo; pluripotency; P21; zygotic genome activation

Funding

  1. National Natural Science Foundation of China [31,760,333]
  2. Key Technology Research Plan Project of Inner Mongolia Autonomous Region [2021GG0153]
  3. Science and Technology Major Project of Inner Mongolia Autonomous Region of China [2019ZD031]

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The miR-290 family plays a critical role in zygotic genome activation by directly targeting the 3'-UTR of p21 mRNA.
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. Summary sentence MiR-290 family has critical role in zygotic genome activation by directly targeting the 3'-UTR of p21 mRNA. [GRAPHICS]

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