In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 6 ( 2023-6-13), p. e3002097-
Abstract:
Identifying host genes essential for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of Coronavirus Disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify proviral host factors for highly pathogenic human coronaviruses. Few host factors were required by diverse coronaviruses across multiple cell types, but DYRK1A was one such exception. Although its role in coronavirus infection was previously undescribed, DYRK1A encodes D ual Specificity T y rosine Phosphorylation R egulated K inase 1A and is known to regulate cell proliferation and neuronal development. Here, we demonstrate that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) entry. We show that DYRK1A promotes DNA accessibility at the ACE2 promoter and a putative distal enhancer, facilitating transcription and gene expression. Finally, we validate that the proviral activity of DYRK1A is conserved across species using cells of nonhuman primate and human origin. In summary, we report that DYRK1A is a novel regulator of ACE2 and DPP4 expression that may dictate susceptibility to multiple highly pathogenic human coronaviruses.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002097
DOI:
10.1371/journal.pbio.3002097.g001
DOI:
10.1371/journal.pbio.3002097.g002
DOI:
10.1371/journal.pbio.3002097.g003
DOI:
10.1371/journal.pbio.3002097.g004
DOI:
10.1371/journal.pbio.3002097.g005
DOI:
10.1371/journal.pbio.3002097.s001
DOI:
10.1371/journal.pbio.3002097.s002
DOI:
10.1371/journal.pbio.3002097.s003
DOI:
10.1371/journal.pbio.3002097.s004
DOI:
10.1371/journal.pbio.3002097.s005
DOI:
10.1371/journal.pbio.3002097.s006
DOI:
10.1371/journal.pbio.3002097.s007
DOI:
10.1371/journal.pbio.3002097.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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