Promoter-associated lncRNA pancEIF4G3 regulates embryonic genome activation in porcine early embryos

Long non-coding RNAs (lncRNA) play important regulatory roles during embryonic genome activation (EGA) in porcine early embryonic development. However, whether promoter-associated lncRNAs exert key functions in EGA and their underlying regulatory mechanisms remain largely unclear in pigs. In this study, we identified a highly expressed promoter-associated long non-coding RNA during the 4-cell stage of porcine embryos and named it pancEIF4G3. pancEIF4G3 is a nuclear-localized lncRNA that lacks protein-coding capacity and exhibits an expression pattern similar to its neighboring gene EIF4G3. The study found that interference with either pancEIF4G3 or EIF4G3 led to developmental arrest of porcine embryos at the 4-cell stage, indicating their crucial role in early embryogenesis. Further investigation revealed that pancEIF4G3, which is located upstream of EIF4G3, regulates both its RNA and protein expression levels through binding to OGG1. Downregulation of pancEIF4G3 and EIF4G3 resulted in reduced chromatin accessibility, decreased nascent RNA synthesis, and significant downregulation of multiple EGA marker genes and core transcription factors. In summary, this study is the first to reveal a novel mechanism in porcine early embryos whereby the promoter-associated lncRNA pancEIF4G3 regulates the expression of the translation initiation factor EIF4G3, thereby influencing the process of embryonic genome activation. This finding enriches the regulatory network of early embryonic development in pigs and also provides a potential molecular target for optimizing in vitro embryo culture and reproductive techniques.