Translation regulatory factor BZW1 regulates preimplantation embryo development and compaction by restricting global non-AUG Initiation

Jue Zhang, Shuai-Bo Pi, Nan Zhang, Jing Guo, Wei Zheng, Lizhi Leng, Ge Lin () and Heng-Yu Fan ()
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Jue Zhang: Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA
Shuai-Bo Pi: Zhejiang University
Nan Zhang: Central South University
Jing Guo: Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA
Wei Zheng: Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA
Lizhi Leng: Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA
Ge Lin: Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA
Heng-Yu Fan: Zhejiang University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Protein synthesis is an essential step in gene expression during the development of mammalian preimplantation embryos. This is a complex and highly regulated process. The accuracy of the translation initiation codon is important in various gene expression programs. However, the mechanisms that regulate AUG and non-AUG codon initiation in early embryos remain poorly understood. BZW1 is a key factor in determining the mRNA translation start codon. Here, we show that BZW1 is essential for early embryonic development in mice. Bzw1-knockdown embryos fail to undergo compaction, and show decreased blastocyst formation rates. We also observe defects in the differentiation capacity and implantation potential after Bzw1 interference. Further investigation revealed that Bzw1 knockdown causes the levels of translation initiation with CUG as the start codon to increase. The decline in BZW1 levels result in a decrease in protein synthesis in preimplantation embryos, whereas the total mRNA levels are not altered. Therefore, we concluded that BZW1 contributes to protein synthesis during early embryonic development by restricting non-AUG translational initiation.

Date: 2022
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DOI: 10.1038/s41467-022-34427-x

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