iScience
Volume 25, Issue 7, 15 July 2022, 104614
Journal home page for iScience

Article
Intronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune signaling and oxidative stress pathways

https://doi.org/10.1016/j.isci.2022.104614Get rights and content
Under a Creative Commons license
open access

Highlights

  • Lung expression patterns suggest ACE2 regulation by immune and oxidative signaling

  • CRISPR deletion of intronic regulatory elements (REs) alters ACE2 expression

  • Effects of RE deletion are modified by immune stimulation and oxidative stress

  • Propose two mechanisms for regulating ACE2 at baseline and after immune challenge

Summary

The angiotensin-converting enzyme 2 (ACE2) protein is a key catalytic regulator of the renin-angiotensin system (RAS), involved in fluid homeostasis and blood pressure modulation. ACE2 also serves as a cell-surface receptor for some coronaviruses such as SARS-CoV and SARS-CoV-2. Improved characterization of ACE2 regulation may help us understand the effects of pre-existing conditions on COVID-19 incidence, as well as pathogenic dysregulation following viral infection. Here, we perform bioinformatic analyses to hypothesize on ACE2 gene regulation in two different physiological contexts, identifying putative regulatory elements of ACE2 expression. We perform functional validation of our computational predictions via targeted CRISPR-Cas9 deletions of these elements in vitro, finding them responsive to immune signaling and oxidative-stress pathways. This contributes to our understanding of ACE2 gene regulation at baseline and immune challenge. Our work supports pursuit of these putative mechanisms in our understanding of infection/disease caused by current, and future, SARS-related viruses such as SARS-CoV-2.

Subject areas

Biological sciences
Molecular biology
Immunology
Virology

Data and code availability

  • Accessions for publicly-available datasets used in this study are described in previous publications and in the key resources table.

  • This paper does not report original code. Code used to generate figures is available upon reasonable request from the lead contact.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

  • Additional Supplemental Items are available from Mendeley Data: https://data.mendeley.com/datasets/wmv6f24xm2/1.

Richard, Daniel (2022) “Intronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune signaling and oxidative stress pathways - Richard et al., 2022”, Mendeley Data, V1: https://doi.org/10.17632/wmv6f24xm2.1.

Cited by (0)

8

These authors contributed equally

9

Lead contact