Dataset Information

Genome-wide profiling of host-encoded circular RNAs highlights their potential role during the Japanese encephalitis virus-induced neuroinflammatory response.

ABSTRACT:

Background

Japanese encephalitis virus (JEV) is one of the common causes of acute encephalitis in humans. Japanese encephalitis is characterized by the uncontrolled release of inflammatory cytokines, which ultimately results in neuronal cell damage. In recent years, with the advancement of high-throughput sequencing technology, studies have shown that circRNAs, by competing with endogenous miRNAs, play a vital role in the pathology of CNS diseases. However, it is unknown whether circRNAs participate in JEV-induced neuroinflammation.

Results

By employing Illumina RNA-sequencing, we identified 180 circRNAs and 58 miRNAs that showed significant differential expression in JEV-infected mice brain tissues. The functional enrichment analyses revealed that these differentially regulated circRNAs were predominantly related to neurotransmission, histone modifications, transcription misregulation, and inflammation-associated calcium signaling pathway. Our established competing endogenous RNA (ceRNA) interaction network suggested the correlation of several circRNAs, miRNAs, and mRNAs in regulating the inflammatory response during JEV infection. Among the predicted interactions, the correlation between circ_0000220, miR-326-3p, and BCL3/MK2/TRIM25 mRNAs was experimentally validated by knockdown or overexpression of the non-coding RNA entities in cultured mouse microglia. The knockdown of circ_0000220 or overexpression of miR-326-3p caused a lower production of JEV-induced inflammatory cytokines.

Conclusions

Conclusively, our study provides new insights into the host response to JEV infection and proposes the circRNA-targeting therapeutic interventions to rein in Japanese encephalitis.

SUBMITTER: Li Y

PROVIDER: S-EPMC7301528 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Genome-wide profiling of host-encoded circular RNAs highlights their potential role during the Japanese encephalitis virus-induced neuroinflammatory response.

Li Yunchuan Y Ashraf Usama U Chen Zheng Z Zhou Dengyuan D Imran Muhammad M Ye Jing J Chen Huanchun H Cao Shengbo S

BMC genomics 20200618 1

<h4>Background</h4>Japanese encephalitis virus (JEV) is one of the common causes of acute encephalitis in humans. Japanese encephalitis is characterized by the uncontrolled release of inflammatory cytokines, which ultimately results in neuronal cell damage. In recent years, with the advancement of high-throughput sequencing technology, studies have shown that circRNAs, by competing with endogenous miRNAs, play a vital role in the pathology of CNS diseases. However, it is unknown whether circRNAs ...[more]

PMID: 32552669

Similar Datasets

Project description:Covalently closed circular RNAs are neoteric to the eukaryotic family of long non-coding RNAs emerging as a result of 5'-3' backsplicing from exonic, intronic, or intergenic regions spanning the parental gene. Owing to their unique structure and stability, circular RNAs have a multitude of functional properties such as micro-RNA and protein sponges, direct and indirect modulators of gene expression, protein translation, and many unproven activities apart from being potential biomarkers. However, due to their low abundance, most of the global circular RNA identification is carried out by high-throughput NGS-based approaches requiring millions of sequencing reads. This lag in methodological advancements demands for newer, more refined, and efficient identification techniques. Here, we aim to show an improved version of our previously reported template-dependent multiple displacement amplification (tdMDA)-NGS method by superimposing the ribosomal depletion step and use of H minus reverse transcriptase and RNase H. Implication of tdMDA using highly replicative Phi29 DNA polymerase after minimizing the linear and ribosomal RNA content further intensifies its detection limit toward even the abysmally expressing circular RNA at a low NGS depth, thereby decreasing the cost of identifying a single circular RNA. A >11-fold and >6-fold increase in total circular RNA was identified from the improved-tdMDA-NGS method over the traditional method of circRNA sequencing using DCC and CIRI2 pipelines, respectively, from Oryza sativa subsp. Indica. Furthermore, the reliability of the improved-tdMDA-NGS method was also asserted in HeLa cell lines, showing a significant fold difference in comparison with the existing traditional method of circRNA sequencing. Among the identified circular RNAs, a significant percentage from both rice (∼58%) and HeLa cell lines (∼84%) is found to be matched with the previously reported circular RNAs, suggesting that the improved-tdMDA-NGS method can be adapted to detect and characterize the circular RNAs from different biological systems.

Dataset Information

Genome-wide profiling of host-encoded circular RNAs highlights their potential role during the Japanese encephalitis virus-induced neuroinflammatory response.

Background

Results

Conclusions

Publications

Genome-wide profiling of host-encoded circular RNAs highlights their potential role during the Japanese encephalitis virus-induced neuroinflammatory response.

Similar Datasets

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