Omics · study · 2026
Effect of CSDE1 knockout in RAW264.7 cells on gene expression following SARS CoV-2 RNA stimulation
Listed in NCBI GEO
RIG-I-like receptors (RLRs)-mediated antiviral innate immunity is critical for restricting RNA viral infection.
Description
The liquid-liquid phase separation (LLPS) is crucial for fine-tuning cellular signaling transduction, but whether RLR signaling is under the regulation of LLPS remains largely enigmatic. In this study, we identify the RNA-binding protein cold shock domain containing E1 (CSDE1) as a novel negative regulator of RLR signaling to promote viral immune evasion.
The deficiency of CSDE1 in macrophages results in increased expression of type I interferon and ISGs following RNA viral infection. Mice with macrophage conditional knockout of CSDE1 are less susceptible to RNA viral infection. CSDE1, with multivalent CSD motifs, forms bio-molecular condensates with long single stranded RNA (ssRNA).
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The LLPS of CSDE1 sequesters viral RNA from recognition by RLRs to inhibit RLR signaling. Notably, virus-activated TBK1 kinase mediates the phosphorylation of CSDE1 to disturb its LLPS. Consequently, phosphorylation of CSDE1 relieves its suppression of RLR signaling.
Intriguingly, LLPS of CSDE1 promotes the condensation of the SARS-CoV-2 nucleocapsid (N) protein and is critical for the anti-interferon activity of the N protein. Repression of CSDE1 condensation with screened compound abrogates the CSDE1 LLPS and subsequent replication of SARS-CoV-2. Overall, our study delineates a novel regulatory mechanism of RLR signaling transduction by phosphorylation-modulated LLPS of CSDE1, indicating that targeting the LLPS of CSDE1 is a promising strategy for RNA viral infection treatment.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299410 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299410 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1274384 ncbi.nlm.nih.gov/bioproject/PRJNA1274384 ↗
project · from NCBI GEO
- PubMed 42049720 pubmed.ncbi.nlm.nih.gov/42049720 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE299410 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |