Cocaine-regulated microRNA miR-124 controls poly (ADP-ribose) polymerase-1 expression in neuronal cells.
3' Untranslated Regions
/ genetics
Animals
Binding Sites
/ genetics
Cell Line, Tumor
Cocaine
/ pharmacology
Dopaminergic Neurons
/ drug effects
Down-Regulation
/ drug effects
Gene Knockdown Techniques
Humans
Injections, Intraperitoneal
Male
Mice
MicroRNAs
/ genetics
Models, Animal
Mutation
Nucleus Accumbens
/ cytology
Poly (ADP-Ribose) Polymerase-1
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 07 2020
08 07 2020
Historique:
received:
12
12
2019
accepted:
18
06
2020
entrez:
10
7
2020
pubmed:
10
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
MiR-124 is a highly expressed miRNA in the brain and regulates genes involved in neuronal function. We report that miR-124 post-transcriptionally regulates PARP-1. We have identified a highly conserved binding site of miR-124 in the 3'-untranslated region (3'UTR) of Parp-1 mRNA. We demonstrate that miR-124 directly binds to the Parp-1 3'UTR and mutations in the seed sequences abrogate binding between the two RNA molecules. Luciferase reporter assay revealed that miR-124 post-transcriptionally regulates Parp-1 3'UTR activity in a dopaminergic neuronal cell model. Interestingly, the binding region of miR-124 in Parp-1 3'UTR overlapped with the target sequence of miR-125b, another post-transcriptional regulator of Parp-1. Our results from titration and pull-down studies revealed that miR-124 binds to Parp-1 3'UTR with greater affinity and confers a dominant post-transcriptional inhibition compared to miR-125b. Interestingly, acute or chronic cocaine exposure downregulated miR-124 levels concomitant with upregulation of PARP-1 protein in dopaminergic-like neuronal cells in culture. Levels of miR-124 were also downregulated upon acute or chronic cocaine exposure in the mouse nucleus accumbens (NAc)-a key reward region of brain. Time-course studies revealed that cocaine treatment persistently downregulated miR-124 in NAc. Consistent with this finding, miR-124 expression was also significantly reduced in the NAc of animals conditioned for cocaine place preference. Collectively, these studies identify Parp-1 as a direct target of miR-124 in neuronal cells, establish miR-124 as a cocaine-regulated miRNA in the mouse NAc, and highlight a novel pathway underlying the molecular effects of cocaine.
Identifiants
pubmed: 32641757
doi: 10.1038/s41598-020-68144-6
pii: 10.1038/s41598-020-68144-6
pmc: PMC7343862
doi:
Substances chimiques
3' Untranslated Regions
0
MIRN124 microRNA, human
0
MicroRNAs
0
Mirn124 microRNA, mouse
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
11197Subventions
Organisme : NIH HHS
ID : MD007593
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA007359
Pays : United States
Organisme : NIDA NIH HHS
ID : R00 DA042111
Pays : United States
Organisme : NIDA NIH HHS
ID : R03 DA030896
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR000447
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA014133
Pays : United States
Organisme : NIH HHS
ID : MD007586
Pays : United States
Organisme : NIDA NIH HHS
ID : R00 DA024558
Pays : United States
Organisme : NIDA NIH HHS
ID : K99 DA024558
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136740
Pays : United States
Organisme : NIMHD NIH HHS
ID : G12 MD007586
Pays : United States
Organisme : NIDA NIH HHS
ID : P01 DA047233
Pays : United States
Organisme : NIDA NIH HHS
ID : R24 DA021471
Pays : United States
Organisme : NIDA NIH HHS
ID : R24 DA036420
Pays : United States
Organisme : NIH HHS
ID : DA042111
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI122960
Pays : United States
Organisme : NIDA NIH HHS
ID : R03 DA033892
Pays : United States
Organisme : NCRR NIH HHS
ID : TL1 RR024978
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA042348
Pays : United States
Organisme : NIH HHS
ID : DA008227
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI110527
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007593
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA041349
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NCRR NIH HHS
ID : U54 RR026140
Pays : United States
Organisme : NIDA NIH HHS
ID : R03 DA037779
Pays : United States
Organisme : NIDA NIH HHS
ID : K99 DA042111
Pays : United States
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