The circular RNA Edis regulates neurodevelopment and innate immunity

Xiong, Xiao-Peng; Liang, Weihong; Liu, Wei; Xu, Shiyu; Li, Jian‐Liang; Tito, Antonio Joel; Situ, Julia; Martinez, Daniel A.; Wu, Chunlai; Perera, Ranjan J.; Zhang, Sheng; Zhou, Rui

doi:10.1371/journal.pgen.1010429

PLoS Genet

2022

DOI: 10.1371/journal.pgen.1010429

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The circular RNA Edis regulates neurodevelopment and innate immunity

Xiao-Peng Xiong

¹

,

Weihong Liang

²

,

Wei Liu

³

et al.

Abstract: Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We identify and validate a collection of circRNAs in Drosophila, and show that depletion of the brain-enriched circRNA Edis (circ_Ect4) causes hyperactivation of antibacterial innate immunity both in cultured cells and in vivo. Notably, Edis depleted flies display heightened resistance to bacterial infection and enhanced pathogen clearance. Conversely, ectopic Edis expression blocks innate i… Show more

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Cited by 15 publications

(25 citation statements)

References 79 publications

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“…To further explore the role of Relish in regulating castor expression, we tested the expression of castor gene in response to Edis depletion in cultured cells. Consistent with our recent study [ 39 ], we detected an increase in Dpt RNA levels upon Edis depletion in S2 cells. Importantly, levels of castor were also similarly higher in Edis knockdown cells than in control cells ( Fig 6D ).…”

Section: Resultssupporting

confidence: 93%

“…Among the tissues/organs examined, including hemocytes, salivary gland, gut, body wall muscle, and fat body, Edis was most prominently enriched in the brain ( Fig 1A ). This is consistent with the notion that circRNAs are enriched in the nervous system [ 22 , 23 , 39 ]. To further visualize the localization pattern of Edis within the brain, RNA fluorescence in situ hybridization assay was performed.…”

Section: Resultssupporting

confidence: 92%

“…In addition, we crossed Elav-Gal4 with UAS-laccase2-Edis flies to drive Edis expression in neurons. We find that restoring Edis expression can rescue the neurodevelopmental phenotypes elicited by Edis knockdown [ 39 ], thereby demonstrating the functional relevance of overexpressed Edis . We therefore employed a similar experimental setting to examine whether overexpressed Edis impacts neuronal development.…”

Section: Resultsmentioning

confidence: 98%

“…Recently, we show that overexpression of Edis suppressed the IMD innate immunity signaling pathway both in cultured cells and in vivo [ 39 ]. In addition, we crossed Elav-Gal4 with UAS-laccase2-Edis flies to drive Edis expression in neurons.…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

A circular RNA Edis-Relish-castor axis regulates neuronal development in Drosophila

Liu

¹

,

Liang

²

,

Xiong

³

et al. 2022

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…To further explore the role of Relish in regulating castor expression, we tested the expression of castor gene in response to Edis depletion in cultured cells. Consistent with our recent study [ 39 ], we detected an increase in Dpt RNA levels upon Edis depletion in S2 cells. Importantly, levels of castor were also similarly higher in Edis knockdown cells than in control cells ( Fig 6D ).…”

Section: Resultssupporting

confidence: 93%

“…Among the tissues/organs examined, including hemocytes, salivary gland, gut, body wall muscle, and fat body, Edis was most prominently enriched in the brain ( Fig 1A ). This is consistent with the notion that circRNAs are enriched in the nervous system [ 22 , 23 , 39 ]. To further visualize the localization pattern of Edis within the brain, RNA fluorescence in situ hybridization assay was performed.…”

Section: Resultssupporting

confidence: 92%

“…In addition, we crossed Elav-Gal4 with UAS-laccase2-Edis flies to drive Edis expression in neurons. We find that restoring Edis expression can rescue the neurodevelopmental phenotypes elicited by Edis knockdown [ 39 ], thereby demonstrating the functional relevance of overexpressed Edis . We therefore employed a similar experimental setting to examine whether overexpressed Edis impacts neuronal development.…”

Section: Resultsmentioning

confidence: 98%

“…Recently, we show that overexpression of Edis suppressed the IMD innate immunity signaling pathway both in cultured cells and in vivo [ 39 ]. In addition, we crossed Elav-Gal4 with UAS-laccase2-Edis flies to drive Edis expression in neurons.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

A circular RNA Edis-Relish-castor axis regulates neuronal development in Drosophila

Liu

¹

,

Liang

²

,

Xiong

³

et al. 2022

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Previous studies show that select circRNAs associate with miRNAs and impact miRNA levels and/or function, 28 , 30 , 45 encode functional proteins, 31 , 32 , 46 , 47 or directly interact with proteins. 47 , 48 To gain insight into the mechanism underlying circATP8B(2) function, we first tested the miRNA-binding and protein-coding hypotheses by performing AGO1 and ribosomal protein RpL22 RNA immunoprecipitation (RIP), respectively.…”

Section: Resultsmentioning

confidence: 99%

The circular RNA circATP8B(2) regulates ROS production and antiviral immunity in Drosophila

Liang

¹

,

Liu

²

,

Xiong

³

et al. 2024

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Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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