# RNA-Binding Proteins in the Regulation of Vascular Inflammation and Immunity

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2024 · $534,209

## Abstract

Inflammation is designed to destroy, disable, or contain pathogenic invaders, but must be controlled to
avoid destruction of key host systems, like the vasculature. When the interaction between immune cells and
the vasculature goes awry, it can contribute to vascular lesions in aneurysm, atherosclerosis, and other
diseases. Our study of the interactions between innate immune cells and the arterial wall in models of
atherosclerosis – a sterile and chronic injury process with a critical inflammatory component – has revealed
broad regulation of alternative splicing responses that change the extracellular composition of the inflamed
intima and the behavior of recruited immune cells that protect the arterial wall from damage. Guided by
these data and novel in vitro CRISPR screens to probe the function of RNA binding proteins (RBP) in the
regulation endothelial inflammation, we have discovered a set of RBP responsive to innate immune cell
recruitment that are critical in orchestrating the activation of the endothelium through NFkB signaling. Here,
we test the hypothesis that one of these RBP, Elavl1, coordinates alternative splicing in the arterial intima in
response to innate immune cell recruitment to regulate chronic immune functions (Aim 1). In seeking a
deeper understanding of this immune-regulatory system, we made the unexpected discovery that, like
Elavl1, many RBP strongly bind to transposable element (TE) sequences inserted within genes and their
RNA transcripts (p<0.0001). While most TE are inactive, these vestigial TE sequences account for ~45% of
our genome, are found in nearly all genes, and can provide cryptic splice sites in transcripts that depend on
RBP activity. Thus, we aim to define the family of TE-binding RBP, to understand their regulation during
inflammatory responses, and their impact on splicing patterns and inflammatory responses through binding
to TE (Aim 2). The completion of these aims will provide new insight into the contribution of endothelial
alternative splicing responses to inflammation in chronic inflammatory states, and the contribution of
pervasive TE-derived sequence to transcript regulation through RBP that bind them, providing new avenues
to understand and treat chronic inflammation in the cardiovascular system.

## Key facts

- **NIH application ID:** 10810862
- **Project number:** 5R01HL150362-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Patrick Andries Murphy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $534,209
- **Award type:** 5
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810862

## Citation

> US National Institutes of Health, RePORTER application 10810862, RNA-Binding Proteins in the Regulation of Vascular Inflammation and Immunity (5R01HL150362-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10810862. Licensed CC0.

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