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Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses

ABSTRACT: Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses

PROVIDER: PRJNA883588 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21681911_1.fastq.gz	Fastqsanger.gz
	SRR21681911_2.fastq.gz	Fastqsanger.gz
	SRR21681912_1.fastq.gz	Fastqsanger.gz
	SRR21681912_2.fastq.gz	Fastqsanger.gz
	SRR21681913_1.fastq.gz	Fastqsanger.gz

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Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses [RNAseq]

Project description:We demonstrate that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and 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 monkey and human origin and an in vivo mouse model.

2023-04-02 | GSE213998 | GEO

Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses [ATACseq]

2023-04-02 | GSE213997 | GEO

Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses [ATACseq]

Project description:Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses [ATACseq]

| PRJNA883595 | ENA

Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses [RNAseq]

Project description:Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses [RNAseq]

| PRJNA883592 | ENA

Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-02 | GSE213999 | GEO

DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner.

Project description: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 Dual Specificity Tyrosine Phosphorylation Regulated Kinase 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.

| S-EPMC10263356 | biostudies-literature

The DYRK1A kinase positively regulates angiogenic responses in endothelial cells

Project description:Angiogenesis is a highly regulated process essential for organ development and maintenance, and its deregulation contributes to inflammation, cardiac disorders and cancer. The Ca2+/Nuclear Factor of Activated T-cells (NFAT) signaling pathway is central to endothelial cell angiogenic responses, and it is activated by stimuli like the vascular endothelial growth factor A (VEGF). NFAT phosphorylation by dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) is thought to be an inactivating event. Contrary to expectations, we show that the DYRK family member DYRK1A positively regulates VEGF-dependent NFAT transcriptional responses in primary endothelial cells. DYRK1A silencing reduces intracellular Ca2+ influx in response to VEGF, which dampens NFAT activation. The effect is exerted at the level of VEGFR2 accumulation leading to impairment in PLCg1 activation. Notably, Dyrk1a heterozygous mice show defects in developmental retinal vascularization. Our data establish a regulatory circuit, DYRK1A/ Ca2+/NFAT, to fine-tune endothelial cell proliferation and angiogenesis.

2018-03-22 | GSE112172 | GEO

Chromatin-wide profiling of the protein kinase DYRK1A reveals a role as a transcriptional activator of cell growth related genes

Project description:DYRK1A is a dosage-sensitive protein kinase that fulfills key roles during development and in tissue homeostasis, and its dysregulation results in human pathologies. DYRK1A is present in both the nucleus and cytoplasm of mammalian cells, although its nuclear function remains unclear. Genome-wide analysis of DYRK1A-associated loci reveals that the kinase is recruited preferentially to promoters of genes actively transcribed by RNA polymerase II (RNAPII), which are functionally associated with translation, RNA processing and cell cycle. DYRK1A-bound promoter sequences are highly enriched in a conserved palindromic motif, which is necessary to drive DYRK1A-dependent transcriptional activation. DYRK1A phosphorylates the carboxy-terminal domain (CTD) of RNAPII at Ser2 and Ser5. Depletion of DYRK1A results in reduced association of RNAPII at the target promoters as well as hypophosphorylation of the CTD of RNAPII along the target gene bodies. Accordingly, we propose that DYRK1A acts as a transcriptional regulator by acting as a novel CTD kinase. Occupancy of the kinase DYRK1A in two different cell lines and in two different growing conditions.

2015-03-11 | E-GEOD-63712 | biostudies-arrayexpress

Chromatin-wide profiling of the protein kinase DYRK1A reveals a role as a transcriptional activator of cell growth related genes

2015-03-11 | GSE63712 | GEO

Expression data in the cerebral cortex of postnatal Dyrk1a+/+ and Dyrk1a+/- mice

Project description:DYRK1A is a protein kinase with several roles in brain development. This kinase is involved in two intellectual disability syndromes: Down syndrome and DYRK1A haploinsufficiency syndrome. The Dyrk1a+/- mouse is a model for DYRK1A haploinsufficiency syndrome. We used microarray to evaluate the impact of DYRK1A haploinsufficiency in the development of the cerebral cortex.

2019-03-06 | GSE127707 | GEO

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