RNA binding protein HuR regulated by OIP5-AS1 may be involved in maternal transcript degradation during the human maternal-to-zygotic transition.

BACKGROUND: The maternal-to-zygotic transition (MZT) is a critical process in early human development, involving the degradation of maternal gene transcripts and activation of zygotic genes. Any disruption in the degradation of maternal transcripts may be associated with some reproductive disorders. However, the precise mechanism by which maternal gene transcripts are degraded during this transition remains unclear. RESULTS: Through an analysis of weighted gene co-expression networks, an oocyte-specific module was identified, showing high consistency with the expression pattern of maternal transcripts degraded at the 8-cell stage, which is associated with the cell cycle and transcription factor binding. Within this module, a maternal long non-coding RNA known as OIP5 antisense RNA 1 (OIP5-AS1) was identified. It was observed that OIP5-AS1 can bind to the RNA binding protein human antigen R (HuR), potentially limiting its availability for other mRNAs and contributing to the degradation of maternal transcripts during MZT. Moreover, RNA immunoprecipitation sequencing in human induced pluripotent stem cells (iPSCs) revealed HuR and OIP5-AS1 are likely to tightly bind together and involved in functions related to the cell cycle and transcriptional regulation. Upon knocking down OIP5-AS1 and the ELAVL1 gene, which encodes the HuR protein in human iPSCs, a significant reduction in the expression levels of maternal transcripts was observed, suggesting an essential role of these factors in regulating maternal transcript stability during early development. CONCLUSIONS: The HuR protein plays a critical role in influencing the degradation of maternal transcripts during the MZT in early human embryonic development. Understanding the role of OIP5-AS1 in regulating HuR protein could provide valuable insights into developmental biology and potentially lead to new therapeutic strategies for developmental disorders.