mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development

Abstract

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.

Experimental verification and comprehensive analysis of m7G methylation regulators in the subcluster classification of ischemic stroke

“…CYFIP2 has been shown to play vital regulatory role in the central nervous system (Schaks et al, 2020). NCBP2 and DCPS are believed to be involved in neurogenesis, which may inextricably be associated with IS (Singh et al, 2020;Salamon et al, 2022). However, the specific mode of regulation between them and the IS has not yet been studied.…”