mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development

Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development and mRNA metabolism. However, the role of DcpS and its scavenger decapping activity in neuronal development is unknown. Here, we show that human neurons derived from patients with a DcpS mutation have compromised differentiation and neurite outgrowth. Moreover, in the developing mouse neocortex, DcpS is required for the radial migration, polarity, neurite outgrowth, and identity of developing glutamatergic neurons. Collectively, these findings demonstrate that the scavenger mRNA decapping activity contributes to multiple pivotal roles in neural development and further corroborate that mRNA metabolism and neocortical pathologies are associated with intellectual disability.

Automated summary

Mutations in the gene encoding the scavenger mRNA-decapping enzyme DcpS have been linked to developmental delay and intellectual disability, affecting neuronal differentiation and neurite outgrowth in both human and mouse models. These findings suggest that DcpS plays a crucial role in neural development and further support the association between mRNA metabolism, neocortical pathologies, and intellectual disability.