# A novel class of long non-coding RNA in regulation of the type I interferonresponse

> **NIH NIH F30** · YALE UNIVERSITY · 2021 · $30,891

## Abstract

Project Summary
The mammalian genome is pervasively transcribed to generate a complex non-coding transcriptome. A novel
class of long non-coding RNA (lncRNA) called DoGs for “Downstream-of-Gene”-containing transcripts was
recently discovered. In response to various stressors such as viral infections, DoG RNAs are expressed by
readthrough transcription that continues past the ends of some protein-coding genes for at least 5kb. Remarkably,
this previously unknown RNA species as a group accounts for up to 30% of all intergenic transcripts, yet their
function remains completely unknown. I discovered that innate immune sensing of viral nucleic acids and
activation of the type I interferon (IFN) antiviral response leads to expression of DoG RNAs from thousands of
genes, most notably from the IFN gene itself. I therefore hypothesize that a DoG RNA may function to
regulate its upstream gene of origin, and that this is an essential regulatory process in innate antiviral
responses. Mechanistically I propose that a DoG RNA remodels the chromatin and/or transcriptional
landscape of its upstream gene to achieve a poised state. This would be beneficial for organisms because
rapid responses to viral infections can be achieved. In Aim 1, I will evaluate the role of the DoG RNA from the
Ifnb1 gene (Ifnb1-DoG RNA) in regulating IFN-β expression using genetic, transcriptional, and post-
transcriptional approaches to manipulate DoG RNA levels. In Aim 2, I will investigate the molecular basis of
Ifnb1-DoG RNA function by characterizing the chromatin and transcriptional landscape of the Ifnb1 gene locus.
I will test whether DoG RNA expression affects post-transcriptional processing, epigenetic marks, and chromatin
architecture. In Aim 3, I will determine the physiological importance of DoG RNA in vivo. I will generate Ifnb1-
DoG RNA deficient mice by first generating guide RNA knock-in mice that targets downstream of Ifnb1 and then
by crossing these with dCas9 transgenic mice. I will study the effect of the Ifnb1-DoG RNA on innate immunity
at homeostasis and during viral infections with these mice. The type I IFN response is a critical component of
our antiviral defense mechanism, but can lead to human disease such as type I interferonopathies and systemic
lupus erythematosus when dysregulated. This study aims to advance our understanding of type I IFN regulation
by functionally characterizing a novel class of lncRNAs. Insights gained from this study can potentially be
leveraged to develop improved therapeutics for infectious and IFN-mediated autoimmune diseases.

## Key facts

- **NIH application ID:** 10142037
- **Project number:** 1F30AI157301-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Annsea Park
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,891
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142037

## Citation

> US National Institutes of Health, RePORTER application 10142037, A novel class of long non-coding RNA in regulation of the type I interferonresponse (1F30AI157301-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142037. Licensed CC0.

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