MRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development. (31st August 2021)

• Record Type: Journal Article
• Authors: Salamon, Iva; Palsule, Geeta; Luo, Xiaobing; Roque, Alfonso; Tucai, Shawn; Khosla, Ishan; Volk, Nicole; Liu, Wendy; Cui, Huijuan; Pozzo, Valentina Dal; Zalamea, Petronio; Jiao, Xinfu; D'Arcangelo, Gabriella; Hart, Ronald P; Rasin, Mladen-Roko; Kiledjian, Megerditch
• Is Part Of: Cerebral cortex. Volume 32:Number 7(2022)
• Page Start: 1494
• Page End: 1507
• Publication Date: 2021-08-31
• Subjects: decapping -- glutamatergic neuron -- human induced neurons (iN) -- intellectual disability -- migration -- mRNA decay -- neocortex -- neuron identity -- radial glia; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhab302
• Languages: English
• ISSNs: 1047-3211

Abstract

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.