# Suppression of the type I IFN gene signature by the long non-coding RNA-Lucat-1

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $209,375

## Abstract

Abstract
Only about 2% of the mammalian genome contains genes that are translated into proteins. Yet, the vast
majority of the genome is transcribed as RNA and lncRNAs account for most of these transcripts.
Emerging evidence from our lab and others has defined long non-coding RNAs (lncRNAs) as important
regulators of immunity providing a new perspective on gene regulation in the immune system. To date,
our studies have focused on murine macrophages and studies in animals. This R21 proposal will
advance our understanding of lncRNAs with immunomodulatory functions in human cells, specifically
dendritic cells. We will focus on an intergenic lincRNA- Lucat-1; which we identified as a dynamically
regulated gene in human monocyte derived dendritic cells exposed to Influenza virus, Herpes Simplex
virus and lipopolysaccharide. Using loss and gain of function CRISPr/Cas9-based genome editing
approaches we have found that lucat-1 acts as a negative feedback regulator of type I interferon and
interferon stimulated gene expression in human dendritic cells. Aim 1 will advance our understanding of
this lincRNA by exploring its role in controlling immune gene expression, defining its genomic targets and
identifying its protein binding partners. Aim 2 will characterize the role of lucat-1 in controlling Influenza
virus infection using newly generated lucat-1 KO mice. The underlying hypothesis to be explored in this
proposal is that lucat1 represents a conserved regulatory component of the anti-viral response that acts
to shut down the type I IFN response in infected cells. We propose that nuclear localized chromatin
associated lncRNAs such as Lucat-1 bind the genome to regulate the expression of anti-viral genes. The
versatility of these molecules and their ability to engage protein complexes with gene regulatory capacity
endows these lncRNAs with the capacity to alter the immune response. Detailed mechanistic studies of
how Lucat-1 impact ISG expression in human cells and animals could unveil novel drug targets that
could potentially lead to the development of improved therapeutics for diseases associated with
excessive production of type I IFNs such as lupus.

## Key facts

- **NIH application ID:** 9823857
- **Project number:** 5R21AI142231-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Katherine A. Fitzgerald
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2018-11-16 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823857

## Citation

> US National Institutes of Health, RePORTER application 9823857, Suppression of the type I IFN gene signature by the long non-coding RNA-Lucat-1 (5R21AI142231-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9823857. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*