<i>Ncbp1</i> deficiency affects morula-to-blastocyst transition through lipid metabolic dysregulation

Preimplantation embryogenesis requires precise synchronization of transcriptional activation, mRNA export and translation, and metabolic reprogramming to sustain developmental requirements. Nuclear cap-binding protein 1 (NCBP1), a conserved subunit of the cap-binding complex, has established roles in mRNA processing and export in somatic cells, but its potential functions in preimplantation embryogenesis remain undefined. The spatiotemporal expression dynamics of Ncbp1 were explored on multiple levels. After microinjecting interfering RNA at zygotic stage to knockdown Ncbp1, embryonic developmental competence was evaluated. Co-injection of small interfering RNA and in vitro transcribed Ncbp1 mRNA into the zygote was used to rescue the knockdown phenotype. Further, poly-adenylated RNA-fluorescence in situ hybridization, RNA sequencing, and quantitative proteomics were used to investigate the effects of Ncbp1 knockdown. In addition, oleic acid (OA) supplementation was used to rescue developmental abnormalities. NCBP1 exhibited dynamic spatiotemporal expression coinciding with nuclear-to-cytoplasmic translocation of protein from morula stage. Depletion of Ncbp1 caused morula arrest or fragmentation, accompanied by nuclear poly-adenylated RNA retention and down-regulation of lipid metabolic pathways, notably, stearoyl-CoA desaturase 1 (SCD1), a key enzyme generating monounsaturated OA. Exogenous OA supplementation partially rescued blastocyst formation, implicating NCBP1 in the regulation of SCD1-OA-mediated metabolic homeostasis during morula-to-blastocyst transition. This study illustrates NCBP1 as a mediator that regulates RNA export and lipid homeostasis during early mouse embryo development. Especially NCBP1 regulates the SCD1-OA metabolic pathways, ensuring metabolic flexibility essential for successful morula-to-blastocyst transition, thereby providing new insights into the molecular basis of embryonic developmental competence.