Dataset Information

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition.

ABSTRACT: Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). No correlations between the age of onset of SCZ and linear HOMER1 mRNA were observed, whose expression was mostly unaltered in BD and SCZ postmortem brain. Using in vivo circRNA-specific knockdown of circHomer1a in mouse PFC, we show that it modulates the expression of numerous alternative mRNA transcripts from genes involved in synaptic plasticity and psychiatric disease. Intriguingly, in vivo circHomer1a knockdown in mouse OFC resulted in specific deficits in OFC-mediated cognitive flexibility. Lastly, we demonstrate that the neuronal RNA-binding protein HuD binds to circHomer1a and can influence its synaptic expression in the frontal cortex. Collectively, our data uncover a novel psychiatric disease-associated circRNA that regulates synaptic gene expression and cognitive flexibility.

SUBMITTER: Zimmerman AJ

PROVIDER: S-EPMC7577899 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition.

Zimmerman Amber J AJ Hafez Alexander K AK Amoah Stephen K SK Rodriguez Brian A BA Dell'Orco Michela M Lozano Evelyn E Hartley Brigham J BJ Alural Begüm B Lalonde Jasmin J Chander Praveen P Webster Maree J MJ Perlis Roy H RH Brennand Kristen J KJ Haggarty Stephen J SJ Weick Jason J Perrone-Bizzozero Nora N Brigman Jonathan L JL Mellios Nikolaos N

Molecular psychiatry 20200127 11

Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder ...[more]

PMID: 31988434

Similar Datasets

Project description:BackgroundCircular RNAs (circRNAs) have been shown to play important regulatory roles in a range of both pathological and physiological contexts, but their functions in the context of skin aging remain to be clarified. In the present study, we therefore, profiled circRNA expression profiles in four pairs of aged and non-aged skin samples to identify identifying differentially expressed circRNAs that may offer clinical value as biomarkers of the skin aging process.MethodsWe utilized an RNA-seq to profile the levels of circRNAs in eyelid tissue samples, with qRT-PCR being used to confirm these RNA-seq results, and with bioinformatics approaches being used to predict downstream target miRNAs for differentially expressed circRNAs.ResultsIn total, we identified 571 circRNAs with 348 and 223 circRNAs being up and downregulated that were differentially expressed in aged skin samples compared to young skin samples. The top 10 upregulated circRNAs in aged skin sample were hsa_circ_0123543, hsa_circ_0057742, hsa_circ_0088179, hsa_circ_0132428, hsa_circ_0094423, hsa_circ_0008166, hsa_circ_0138184, hsa_circ_0135743, hsa_circ_0114119, and hsa_circ_0131421. The top 10 reduced circRNAs were hsa_circ_0101479, hsa_circ_0003650, hsa_circ_0004249, hsa_circ_0030345, hsa_circ_0047367, hsa_circ_0055629, hsa_circ_0062955, hsa_circ_0005305, hsa_circ_0001627, and hsa_circ_0008531. Functional enrichment analyses revealed the potential functionality of these differentially expressed circRNAs. The top 3 enriched gene ontology (GO) terms of the host genes of differentially expressed circRNAs are regulation of GTPase activity, positive regulation of GTPase activity and autophagy. The top 3 enriched KEGG pathway ID are Lysine degradation, Fatty acid degradation and Inositol phosphate metabolism. The top 3 enriched reactome pathway ID are RAB GEFs exchange GTP for GDP on RABs, Regulation of TP53 Degradation and Regulation of TP53 Expression and Degradation. Six circRNAs were selected for qRT-PCR verification, of which 5 verification results were consistent with the sequencing results. Moreover, targeted miRNAs, such as hsa-miR-588, hsa-miR-612, hsa-miR-4487, hsa-miR-149-5p, hsa-miR-494-5p were predicted for circRna-miRna interaction networks.ConclusionOverall, these results offer new insights into circRNA expression profiles, potentially highlighting future avenues for research regarding the roles of these circRNAs in the context of skin aging.

Project description:Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Based on these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocular hypertension models were induced by episcleral vein ligation (EVL) and microbead injection in rats. Overall, 15,819 circular RNA were detected. Furthermore, 3,502 differentially expressed circular RNAs verified in both COH rats were identified, of which 691 were upregulated and 2,811 were downregulated. Seven significantly downregulated (both log2FoldChange < -2.5 and adjusted P < 0.001) and seven significantly upregulated (both log2FoldChange > 2.5 and adjusted P < 0.001) circular RNAs were shown. Six target microRNAs aligned with the top 14 circular RNAs were identified. According to the construction of the circular RNA-microRNA network and circBase information, only RNO_CIRCpedia_1775 had the homologous hsa_circ_0023826 in the human genome. The hsa_circ_0023826 and mRNA of the host gene TENM4 (teneurin transmembrane protein 4) were validated in aqueous humor samples of five glaucoma patients and five cataract control patients. The expression of hsa_circ_0023826 showed a significant decrease in glaucoma patients, while TENM4 mRNA showed no significant difference compared to cataract patients (P = 0.024 and P = 0.294, respectively). The results of this study comprehensively characterized the expression profiles of circular RNA in glaucoma-affected eyes, as verified by two different ocular hypertension rat models. Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.

Dataset Information

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition.

Publications

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets