Background: Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells.
Results: We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development.
Conclusions: We reveal the abnormal regulation of these mRNAs in the Fmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.
Keywords: Cerebellum; Cortex; Fmr1-KO mouse; Fragile X protein (FMRP), Upframeshift protein 1 (UPF1); Fragile X syndrome; Hippocampus; Mouse brain development; Nonsense-mediated mRNA decay (NMD).
© 2021. The Author(s).