# Role of Circular RNAs in Innate Immunity and Neuro-development

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

PROJECT SUMMARY
 The goal of the proposed study is to identify and determine the function of circular RNAs
(circRNAs) in innate immunity and neuro-development. Appropriate activation of the immune
response is crucial for host fitness. While effective control of invading pathogens or response to
endogenous stress signals depend on rapid and robust induction of immunity signaling pathways,
prolonged or aberrant activation, either systemically or locally, can lead to pathological conditions
such as autoimmunity, cancer and neurodegeneration. In particular, chronic inflammation in the brain
is associated with impaired neuro-development and function. Thus both the magnitude and duration of
the immune response need to be tightly regulated. Non-coding RNAs (ncRNAs) play a critical role in
modulating antiviral immunity in a wide variety of organisms. Recent advances in deep-sequencing
technology and computational biology have greatly expanded the repertoire of regulatory ncRNAs,
and circRNAs are the latest addition. Besides their unique configurations, circRNAs are distinct from
their canonical linear siblings by harboring frequent exon scrambling events. Originally viewed as
merely by-products of rare “head-to-tail” back-splicing events, circRNAs have recently been
characterized as an abundant class of RNAs in eukaryotes. However, with the exception of only a
handful of circRNAs, the function of the vast majority is unknown. We identified a collection of
circRNAs in Drosophila that are differentially expressed in response to bacterial infection, and our
preliminary studies have implicated the brain-enriched circRNA Edis in innate immunity and neuro-
development. We hypothesize that Edis modulates innate immunity signaling and neuro-development
and function, and propose to employ a combination of genomic, computational, genetic, and
biochemical approaches to establish the function of Edis and elucidate the regulatory mechanism
underlying Edis expression.
 Completion of the proposed study will establish circRNAs as a new class of regulatory ncRNAs,
elucidate the regulatory mechanism of circRNA expression, and determine their function in modulating
innate immunity and neuro-development. This will advance our understanding of their evolutionarily
conserved mammalian counterparts, and provide new insights into the mechanisms underlying the
interplay between innate immunity and neuro-development in physiological and pathological settings.

## Key facts

- **NIH application ID:** 9965749
- **Project number:** 5R01AI140049-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Rui Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2018-08-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965749

## Citation

> US National Institutes of Health, RePORTER application 9965749, Role of Circular RNAs in Innate Immunity and Neuro-development (5R01AI140049-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9965749. Licensed CC0.

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