The Secret Garden of Neuronal circRNAs

Gasparini, Silvia; Licursi, Valerio; Presutti, Carlo; Mannironi, Cecilia

doi:10.3390/cells9081815

Cited by 14 publications

(14 citation statements)

References 157 publications

(305 reference statements)

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“…FEZ1 binds with DISC1 and increases neurite outgrowth in response to NGF (42). Qki can bind with intronic regions and participate in the biogenesis of circRNAs (43). Abnormal expression of Qki might be associated with the observed dysregulation of cricRNAs in schizophrenia (44).…”

Section: Diagnostic Value Of Mirnas In Schizophreniamentioning

confidence: 99%

A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis

et al. 2021

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Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the role of copy number variants (generally deletions) and certain alleles of common single nucleotide polymorphisms in the pathogenesis of schizophrenia. This disorder predominantly follows the polygenic inheritance model. Schizophrenia has also been linked with various alterations in the transcript and protein content of the brain tissue. Recent studies indicate that alterations in non-coding RNAs (ncRNAs) signature underlie a proportion of this dysregulation. High throughput microarray investigations have demonstrated momentous alterations in the expression of long non-coding RNAs (lncRNA) and microRNAs (miRNAs) in the circulation or post-mortem brain tissues of patients with schizophrenia compared with control samples. While Gomafu, PINT, GAS5, TCONS_l2_00021339, IFNG-AS1, FAS-AS1, PVT1, and TUG1 are among down-regulated lncRNAs in schizophrenia, MEG3, THRIL, HOXA-AS2, Linc-ROR, SPRY4-IT1, UCA1, and MALAT1 have been up-regulated in these patients. Moreover, several miRNAs, such as miR-30e, miR-130b, hsa-miR-130b, miR-193a-3p, hsa-miR-193a-3p, hsa-miR-181b, hsa-miR-34a, hsa-miR-346, and hsa-miR-7 have been shown to be dysregulated in blood or brain samples of patients with schizophrenia. Dysregulation of these transcripts in schizophrenia not only provides insight into the pathogenic processes of this disorder, it also suggests these transcripts could serve as diagnostic markers for schizophrenia. In the present paper, we explore the changes in the expression of miRNAs and lncRNAs in patients with schizophrenia.

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Section: Diagnostic Value Of Mirnas In Schizophreniamentioning

confidence: 99%

A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis

et al. 2021

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“…For instance, it remains unclear whether circRNAs act on microRNAs simply by blocking their function and/or by affecting their stability. In this sense, although it has been speculated that circRNAs might trigger TDMD like linear RNAs, this premise was never formally and experimentally tested so far (Gasparini et al , 2020). Our data suggest the opposite: even when expressed at comparable levels, artificial circular RNAs of identical sequence to those of TDMD-inducing linear RNAs, prove incapable of inducing TDMD (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Influence of RNA circularity on Target RNA-Directed MicroRNA Degradation

Whightman

Lukin

Giusti

et al. 2022

Preprint

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Circular RNAs (circRNAs) have been proposed to "sponge" or block microRNAs, a property shared with linear RNAs. Alternatively, certain RNAs induce microRNA destruction through the process of Target RNA-Directed MicroRNA Degradation (TDMD). Whether both linear and circular transcripts are equivalent in driving TDMD is unknown. Here we show that RNA topology is critical for TDMD. Through a novel system that expresses a circRNA while reducing the co-expressed cognate linear RNA, we demonstrate that circRNAs cannot induce TDMD. Interestingly, this is attributed to the circular RNA topology and not to its sequence, which is TDMD-competent in its linear form. Similarly, based on the previous knowledge that CDR1as/ciRS-7 circular RNA protects miR-7 from Cyrano-mediated TDMD, we demonstrate that depletion of CDR1as/CirS-7 reduces mir-7 levels, while overexpression of an artificial linear version of CDR1as/ciRS-7 drives TDMD. By analyzing RNA sequencing data of a neuron differentiation system, we suggest that circRNA-mediated microRNA stabilization is widespread. Our results support a model in which circRNAs, unlike linear mRNAs, lead to a topology-dependent TDMD evasion, aiding in the stabilization of specific microRNAs.

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“…A study in humans comparing the brains of individuals with ASD and controls showed novel circRNAs from the RIMS2 gene, which encodes a presynaptic terminal protein related to vesicular exocytosis [ 94 ]. An ASD mouse model showed different levels of circRNAs in hippocampus [ 95 ]; notably, circRNAs were highly localized in synaptic region [ 94 ]. These results support further investigations into the mechanisms of non-coding RNAs involvement in ASD pathophysiology.…”

Section: Local Translation and Asdmentioning

confidence: 99%

Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder

Joo

Benavides

2021

IJMS

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Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.

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The Secret Garden of Neuronal circRNAs

Cited by 14 publications

References 157 publications

A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis

A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis

Influence of RNA circularity on Target RNA-Directed MicroRNA Degradation

Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder

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