# Mechanosensitive M7G epitranscriptome in endothelial health and disease

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $696,981

## Abstract

Project Summary
 RNA chemical modifications, collectively referred to as the “epitranscriptome”, have recently emerged
as a novel layer of molecular control of gene expression. Most epitranscriptomic studies address N6-
methyladenosine (m6A) of mRNA in human cancers. The molecular identity of endothelial mRNA
epitranscriptome and its potential role in regulating vascular functions remains a major knowledge gap.
 Recent studies suggested that mammalian mRNAs are broadly chemically modified and mRNA
modifications occur in a cell-type and cell-state dependent manner. N6-methyladenosine (m6A), the most
abundant internal (outside of the 5’ cap) methylation in mammalian mRNA, has been linked to critical biological
processes such as proliferation, development, and stem cell differentiation. Only few recent studies addressed
the potential role of mRNA m6A in cardiomyocyte remodeling and endothelial activation. We recently
discovered the presence of a new chemical modification, N7-methylguanosine (m7G) in mammalian mRNA.
Systematic m7G mapping in endothelial mRNA and its potential role in vascular pathophysiology is an
unexplored territory.
 Vascular endothelium is dynamically regulated by blood flow via mechano-transduction mechanisms.
Endothelial activation by disturbed flow contributes to a wide range of vascular diseases. Atherosclerosis
preferentially develops in arterial sites where endothelium is activated by local disturbed flow whereas
unidirectional flow promotes endothelial health. Current atherosclerosis therapies mainly target systematic risk
factors but not the vasculature per se. This underscores the significance and unique opportunity to identify and
target novel mechanosensitive mechanisms in vascular endothelium.
 We have generated very strong data demonstrating that the mRNA m7G is dynamically regulated in
endothelium by hemodynamics. Unidirectional flow (UF) markedly increases m7G but not m6A in endothelial
mRNAs. Moreover, Methyltransferase-Like 7A (METTL7A) is a novel m7G writer governing the UF-induced
mRNA m7G methylation in endothelium. The overall goal of this project is to delineate the novel molecular
mechanisms by which mechano-sensitive METTL7A governs endothelial mRNA m7G and regulates vascular
functions in vitro and in vivo. Moreover, we will devise innovative precision nanomedicine approaches targeting
METTL7A-mediated pathways to treat atherosclerosis.

## Key facts

- **NIH application ID:** 10367181
- **Project number:** 1R01HL155909-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** CHUAN HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $696,981
- **Award type:** 1
- **Project period:** 2021-12-22 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367181

## Citation

> US National Institutes of Health, RePORTER application 10367181, Mechanosensitive M7G epitranscriptome in endothelial health and disease (1R01HL155909-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10367181. Licensed CC0.

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