Experimental upregulation of developmentally downregulated ribosomal protein large subunits 7 and 7A promotes axon regeneration after injury in vivo.
AXON regeneration
Optic nerve injury
RNA-seq
Retinal ganglion cell
Rpl7
Rpl7A
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
19
04
2023
revised:
08
08
2023
accepted:
23
08
2023
pmc-release:
01
10
2024
medline:
8
9
2023
pubmed:
27
8
2023
entrez:
26
8
2023
Statut:
ppublish
Résumé
Ribosomal proteins are involved in neurodevelopment and central nervous system (CNS) disease and injury. However, the roles of specific ribosomal protein subunits in developmental axon growth, and their potential as therapeutic targets for treating CNS injuries, are still poorly understood. Here, we show that ribosomal protein large (Rpl) and small (Rps) subunit genes are substantially (56-fold) enriched amongst the genes, which are downregulated during maturation of retinal ganglion cell (RGC) CNS projection neurons. We also show that Rpl and Rps subunits are highly co-regulated in RGCs, and partially re-upregulated after optic nerve crush (ONC). Because developmental downregulation of ribosomal proteins coincides with developmental decline in neuronal intrinsic axon growth capacity, we hypothesized that Rpl/Rps incomplete re-upregulation after injury may be a part of the cellular response which attempts to reactivate intrinsic axon growth mechanisms. We found that experimentally upregulating Rpl7 and Rpl7A promoted axon regeneration after ONC in vivo. Finally, we characterized gene networks associated with Rpl/Rps, and showed that Rpl7 and Rpl7A belong to the cluster of genes, which are shared between translational and neurodevelopmental biological processes (based on gene-ontology) that are co-downregulated in maturing RGCs during the decline in intrinsic axon growth capacity.
Identifiants
pubmed: 37633482
pii: S0014-4886(23)00195-4
doi: 10.1016/j.expneurol.2023.114510
pmc: PMC10529763
mid: NIHMS1927642
pii:
doi:
Substances chimiques
Ribosomal Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
114510Subventions
Organisme : NEI NIH HHS
ID : R01 EY029739
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA027488
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interests.
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