mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development.
decapping
glutamatergic neuron
human induced neurons (iN)
intellectual disability
mRNA decay
migration
neocortex
neuron identity
radial glia
Journal
Cerebral cortex (New York, N.Y. : 1991)
ISSN: 1460-2199
Titre abrégé: Cereb Cortex
Pays: United States
ID NLM: 9110718
Informations de publication
Date de publication:
30 03 2022
30 03 2022
Historique:
received:
30
04
2021
revised:
08
07
2021
accepted:
12
07
2021
pubmed:
2
9
2021
medline:
5
4
2022
entrez:
1
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34467373
pii: 6360527
doi: 10.1093/cercor/bhab302
pmc: PMC8971079
doi:
Substances chimiques
RNA, Messenger
0
mRNA decapping enzymes
0
Endoribonucleases
EC 3.1.-
DcpS protein, human
EC 3.1.27.-
DcpS protein, mouse
EC 3.1.27.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1494-1507Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM126488
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.
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