Differential Expression of Hippocampal Circular RNAs in the BTBR Mouse Model for Autism Spectrum Disorder.
Animals
Autism Spectrum Disorder
/ genetics
Brain Chemistry
Disease Models, Animal
Gene Expression Profiling
Gene Ontology
Hippocampus
/ metabolism
Humans
Male
Mice, Inbred C57BL
Mice, Inbred Strains
/ genetics
Mice, Mutant Strains
/ genetics
RNA, Circular
/ biosynthesis
RNA, Messenger
/ biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
ASD
Autism
BTBR
Hippocampus
Non-coding RNAs
RNA-seq
circRNAs
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
31
07
2019
accepted:
13
01
2020
pubmed:
6
2
2020
medline:
4
2
2021
entrez:
6
2
2020
Statut:
ppublish
Résumé
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with unknown etiology. Recent experimental evidences suggest the contribution of non-coding RNAs (ncRNAs) in the pathophysiology of ASD. In this work, we aimed to investigate the expression profile of the ncRNA class of circular RNAs (circRNAs) in the hippocampus of the BTBR T + tf/J (BTBR) mouse model and age-matched C57BL/6J (B6) mice. Alongside, we analyzed BTBR hippocampal gene expression profile to evaluate possible correlations between the differential abundance of circular and linear gene products. From RNA sequencing data, we identified circRNAs highly modulated in BTBR mice. Thirteen circRNAs and their corresponding linear isoforms were validated by RT-qPCR analysis. The BTBR-regulated circCdh9 was better characterized in terms of molecular structure and expression, highlighting altered levels not only in the hippocampus, but also in the cerebellum, prefrontal cortex, and amygdala. Finally, gene expression analysis of the BTBR hippocampus pinpointed altered biological and molecular pathways relevant for the ASD phenotype. By comparison of circRNA and gene expression profiles, we identified 6 genes significantly regulated at either circRNA or mRNA gene products, suggesting low overall correlation between circRNA and host gene expression. In conclusion, our results indicate a consistent deregulation of circRNA expression in the hippocampus of BTBR mice. ASD-related circRNAs should be considered in functional studies to identify their contribution to the etiology of the disorder. In addition, as abundant and highly stable molecules, circRNAs represent interesting potential biomarkers for autism.
Identifiants
pubmed: 32020500
doi: 10.1007/s12035-020-01878-6
pii: 10.1007/s12035-020-01878-6
doi:
Substances chimiques
RNA, Circular
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2301-2313Subventions
Organisme : Regione Lazio
ID : 2018-LIFE2020
Organisme : ELIXIR-IIB
ID : Call HPC@Cineca
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