N 4 -acetylcytidine of Nop2 mRNA is required for the transition of morula-to-blastocyst.

Autor: Wang M; Developmental Biology Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China., Cheng R; Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China., He H; Developmental Biology Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China., Han Z; HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China., Zhang Y; Computational Biology Research Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China. zhangtyo@hit.edu.cn., Wu Q; Developmental Biology Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China. kigo@hit.edu.cn.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2023 Sep 28; Vol. 80 (10), pp. 307. Date of Electronic Publication: 2023 Sep 28.
DOI: 10.1007/s00018-023-04955-w
Abstrakt: N-acetyltransferase 10 (NAT10)-mediated N 4 -acetylcytidine (ac 4 C) modification is crucial for mRNA stability and translation efficiency, yet the underlying function in mammalian preimplantation embryos remains unclear. Here, we characterized the ac 4 C modification landscape in mouse early embryos and found that the majority of embryos deficient in ac 4 C writer-NAT10 failed to develop into normal blastocysts. Through single-cell sequencing, RNA-seq, acetylated RNA immunoprecipitation combined with PCR (acRIP-PCR), and embryonic phenotype monitoring, Nop2 was screened as a target gene of Nat10. Mechanistically, Nat10 knockdown decreases the ac 4 C modification on Nop2 mRNA and reduces RNA and protein abundance by affecting the mRNA stability of Nop2. Then, depletion of NOP2 may inhibit the translation of transcription factor TEAD4, resulting in defective expression of the downstream lineage-specific gene Cdx2, and ultimately preventing blastomeres from undergoing the trophectoderm (TE) fate. However, exogenous Nop2 mRNA partially reverses this abnormal development. In conclusion, our findings demonstrate that defective ac 4 C modification of Nop2 mRNA hinders the morula-to-blastocyst transition by influencing the first cell fate decision in mice.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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