A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress.
AGO2
CircRNA
CircSLC8A1
Parkinson's disease
RNA sequencing
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 09 2020
07 09 2020
Historique:
received:
23
12
2019
revised:
23
06
2020
accepted:
25
06
2020
pubmed:
28
7
2020
medline:
19
8
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
Circular RNAs (circRNAs) are brain-abundant RNAs of mostly unknown functions. To seek their roles in Parkinson's disease (PD), we generated an RNA sequencing resource of several brain region tissues from dozens of PD and control donors. In the healthy substantia nigra (SN), circRNAs accumulate in an age-dependent manner, but in the PD SN this correlation is lost and the total number of circRNAs reduced. In contrast, the levels of circRNAs are increased in the other studied brain regions of PD patients. We also found circSLC8A1 to increase in the SN of PD individuals. CircSLC8A1 carries 7 binding sites for miR-128 and is strongly bound to the microRNA effector protein Ago2. Indeed, RNA targets of miR-128 are also increased in PD individuals, suggesting that circSLC8A1 regulates miR-128 function and/or activity. CircSLC8A1 levels also increased in cultured cells exposed to the oxidative stress-inducing agent paraquat but were decreased in cells treated with the neuroprotective antioxidant regulator drug Simvastatin. Together, our work links circSLC8A1 to oxidative stress-related Parkinsonism and suggests further exploration of its molecular function in PD.
Identifiants
pubmed: 32715657
doi: 10.15252/emmm.201911942
pmc: PMC7507321
doi:
Substances chimiques
MicroRNAs
0
RNA, Circular
0
Banques de données
GEO
['GSE133101']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e11942Subventions
Organisme : Israeli Ministry of Science, Technology and Space
ID : 53140
Pays : International
Organisme : Michael J. Fox Foundation for Parkinson's Research (MJFF)
ID : MJFF11183
Pays : International
Organisme : NIA NIH HHS
ID : R01 AG057700
Pays : United States
Organisme : Edmond and Lily Safra Center of Brain Sciences (ELSC)
Pays : International
Organisme : The Netherlands Brain Bank (NBB)
Pays : International
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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