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

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.

Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population

“…Abnormal expression of this gene is associated with a variety of cancers [ 61 , 62 ]. In addition, BZW1 , as a translation initiation regulation factor, plays an important role in preimplantation embryo protein synthesis [ 63 ]. However, its association with COPD remains to be studied.…”

Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications

“…It was observed that before the 8-cell embryo polarization, ezrin was uniformly distributed over the entire cell surface. Once ezrin was phosphorylated, it aggregated from the cell junctions to the apical region, causing the microvilli to also aggregate in the apical region, indicating that phosphorylation of ezrin threonine-567 is necessary for the redistribution of embryo polarization ( Yildirim et al, 2021 ; Zhang et al, 2022b ). Recent studies have revealed that transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) can recruit ezrin proteins to localize to the membrane and promote the polarized growth of apical protein clusters, which eventually leads to apical protein centration.…”