mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development
Open Access
- 31 August 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Cerebral Cortex
- Vol. 32 (7), 1494-1507
- https://doi.org/10.1093/cercor/bhab302
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.Funding Information
- National Institutes of Health (NS075367, GM126488)
This publication has 57 references indexed in Scilit:
- Rapid Single-Step Induction of Functional Neurons from Human Pluripotent Stem CellsNeuron, 2013
- Activation of 5′-3′ exoribonuclease Xrn1 by cofactor Dcs1 is essential for mitochondrial function in yeastProceedings of the National Academy of Sciences of the United States of America, 2012
- Transcriptional co-regulation of neuronal migration and laminar identity in the neocortexDevelopment, 2012
- Development and Evolution of the Human NeocortexCell, 2011
- Evolution of the neocortex: a perspective from developmental biologyNature Reviews Neuroscience, 2009
- DcpS scavenger decapping enzyme can modulate pre-mRNA splicingRNA, 2008
- The radial edifice of cortical architecture: From neuronal silhouettes to genetic engineeringBrain Research Reviews, 2007
- Neuronal subtype specification in the cerebral cortexNature Reviews Neuroscience, 2007
- Function and translational regulation of mRNA in developing axonsSeminars in Cell & Developmental Biology, 2007
- Scavenger Decapping Activity Facilitates 5′ to 3′ mRNA DecayMolecular and Cellular Biology, 2005