LLPS of FXR proteins drives replication organelle clustering for ß-coronaviral proliferation.
J Cell Biol
; 223(6)2024 06 03.
Article
in En
| MEDLINE
| ID: mdl-38587486
ABSTRACT
ß-Coronaviruses remodel host endomembranes to form double-membrane vesicles (DMVs) as replication organelles (ROs) that provide a shielded microenvironment for viral RNA synthesis in infected cells. DMVs are clustered, but the molecular underpinnings and pathophysiological functions remain unknown. Here, we reveal that host fragile X-related (FXR) family proteins (FXR1/FXR2/FMR1) are required for DMV clustering induced by expression of viral non-structural proteins (Nsps) Nsp3 and Nsp4. Depleting FXRs results in DMV dispersion in the cytoplasm. FXR1/2 and FMR1 are recruited to DMV sites via specific interaction with Nsp3. FXRs form condensates driven by liquid-liquid phase separation, which is required for DMV clustering. FXR1 liquid droplets concentrate Nsp3 and Nsp3-decorated liposomes in vitro. FXR droplets facilitate recruitment of translation machinery for efficient translation surrounding DMVs. In cells depleted of FXRs, SARS-CoV-2 replication is significantly attenuated. Thus, SARS-CoV-2 exploits host FXR proteins to cluster viral DMVs via phase separation for efficient viral replication.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA-Binding Proteins
/
Fragile X Mental Retardation Protein
/
SARS-CoV-2
/
COVID-19
/
Liposomes
Limits:
Humans
Language:
En
Journal:
J Cell Biol
Year:
2024
Document type:
Article
Country of publication:
United States