A Psychiatric Disease-Related Circular RNA Controls Synaptic Gene Expression and Cognition

Zimmerman, Amber; Hafez, Alexander; Amoah, Stephen; Dell’Orco, Michela; Haggarty, Stephen J.; Brennand, Kristen; Webster, Maree J.; Perrone‐Bizzozero, Nora I.; Brigman, Jonathan L.; Mellios, Nikolaos

doi:10.1016/j.biopsych.2020.02.914

Cited by 19 publications

(84 citation statements)

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“…Dissecting the effects of each miRNA to these interaction networks can advance our understanding of the individual roles played by miRNA sponging in MTLE pathogenesis and identify targets for further research. Future studies should investigate the effects of knocking down these target circRNAs in neuronal cell lines using in vivo circRNA-specific knockdown (Zimmerman et al, 2020) and assessing the subsequent changes in miRNA activity. If unbound miRNAs regulate mRNA translation, quantitative changes in protein expression should result.…”

Section: Figure 4 | (A)mentioning

confidence: 99%

Identification of Specific Circular RNA Expression Patterns and MicroRNA Interaction Networks in Mesial Temporal Lobe Epilepsy

et al. 2020

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Circular RNAs (circRNAs) regulate mRNA translation by binding to microRNAs (miRNAs), and their expression is altered in diverse disorders, including cancer, cardiovascular disease, and Parkinson's disease. Here, we compare circRNA expression patterns in the temporal cortex and hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and healthy controls. Nine circRNAs showed significant differential expression, including circRNA-HOMER1, which is expressed in synapses. Further, we identified miRNA binding sites within the sequences of differentially expressed (DE) circRNAs; expression levels of mRNAs correlated with changes in complementary miRNAs. Gene set enrichment analysis of mRNA targets revealed functions in heterocyclic compound binding, regulation of transcription, and signal transduction, which maintain the structure and function of hippocampal neurons. The circRNA-miRNA-mRNA interaction networks illuminate the molecular changes in MTLE, which may be pathogenic or an effect of the disease or treatments and suggests that DE circRNAs and associated miRNAs may be novel therapeutic targets.

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Section: Figure 4 | (A)mentioning

confidence: 99%

Identification of Specific Circular RNA Expression Patterns and MicroRNA Interaction Networks in Mesial Temporal Lobe Epilepsy

et al. 2020

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“…Recently, using bioinformatical prediction, it has been shown that neuronal HuD protein (ELAVL4) contained AU-rich elements that were attractive for hundreds of mice brain-expressed circRNAs. RNA immunoprecipitation confirmed this finding and showed that approximately 600 mice brain-expressed circRNAs could interact with HuD [ 112 ]; moreover, 226 of them originated from the previously described circHomer1a gene [ 28 ].…”

Section: The Role Of Rna Binding Proteins (Rbps) In Schizophrenia:mentioning

confidence: 90%

“…It has been also shown that neuronal-enriched circHomer1a (host gene, Homer protein homolog 1) apparently played an important role in cognition processes, as its expression was downregulated in SZ postmortem prefrontal cortex (PFC) area of the human brain, while an intronic circCUL4A (host gene, ubiquitin ligase Cullin-4A) was significantly upregulated [ 28 ].…”

Section: The Role Of Circular Rnas Differential Expression In Schimentioning

confidence: 99%

“…Unfortunately, despite the high level of SZ morbidity in different countries (approximately 1.45%), the mechanisms of RNA binding proteins and circular RNA complex interactions and their functional role in SZ pathogenesis remain unclear. A small number of studies that evaluated the differential expression of this type of ncRNAs in the human brain [ 26 , 27 , 28 , 29 ] have demonstrated only the huge potential of these studies.…”

Section: The Role Of Rna Binding Proteins (Rbps) In Schizophrenia:mentioning

confidence: 99%

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The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Nedoluzhko

Gruzdeva

Sharko

et al. 2020

Cells

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Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

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“…There are different subtypes of circRNAs including exonic, intronic and exo-intronic. Exonic circRNAs are mostly localized in the cytoplasm where they act as sponges for microRNAs (miRNAs) and RNA-binding proteins (RBPs), thus inhibiting their interaction with mRNA targets 4,[9][10][11] . In contrast, intronic or exo-intronic circRNAs are mostly localized in the nucleus and have few or no binding sites for miRNAs; instead they function to control transcription 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

Ravanidis

Bougea

Karampatsi

et al. 2020

Preprint

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BackgroundNew noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of PD diagnosis are urgently needed. CircRNAs are highly stable non-coding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function.ObjectivesThe aims of the present study were to identify differentially expressed circRNAs in PBMCs of idiopathic PD patients and explore the competing endogenous RNA networks affected.MethodsEighty-seven circRNAs were initially selected based on relatively high gene expression in the human brain. Over half of these were readily detectable in PBMCs using RT-qPCR. Comparative expression analysis was then performed in PBMCs from sixty controls and sixty idiopathic subjects with PD.ResultsSix circRNAs derived from MAPK9, HOMER1, SLAIN1, DOP1B, REPS1, and PSEN1 transcripts were significantly downregulated in PD patients. The classifier that best distinguished PD consisted of four circRNAs with an AUC of 0.84. CLIP-Seq data revealed that the RNA binding proteins bound by most of the deregulated circRNAs include the neurodegeneration-associated FUS, TDP43, FMR1 and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs had the GOslim categories ‘Protein modification’, ‘Transcription factor activity’ and ‘Cytoskeletal protein binding’ mostly enriched.ConclusionsThis is the first study that identifies circRNAs deregulated in the peripheral blood of PD patients. They may serve as diagnostic biomarkers and since they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected.

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A Psychiatric Disease-Related Circular RNA Controls Synaptic Gene Expression and Cognition

Cited by 19 publications

References 0 publications

Identification of Specific Circular RNA Expression Patterns and MicroRNA Interaction Networks in Mesial Temporal Lobe Epilepsy

Identification of Specific Circular RNA Expression Patterns and MicroRNA Interaction Networks in Mesial Temporal Lobe Epilepsy

The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

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