N terminus of SARS-CoV-2 nonstructural protein 3 interrupts RNA-driven phase separation of N protein by displacing RNA.

ABSTRACT: The connection between SARS-CoV-2 replication-transcription complexes and nucleocapsid (N) protein is critical for regulating genomic RNA replication and virion packaging over the viral life cycle. However, the mechanism that dynamically regulates genomic RNA packaging and replication remains elusive. Here, we demonstrate that the N-terminal domain of SARS-CoV-2 nonstructural protein 3, a core component of viral replication-transcription complexes, binds N protein and displaces RNA in a concentration-dependent manner. This interaction disrupts liquid-liquid phase separation of N protein driven by N protein-RNA interactions which is crucial for virion packaging and viral replication. We also report a high-resolution crystal structure of the nonstructural protein 3 ubiquitin-like domain 1 (U

SUBMITTER: Ke Z 

PROVIDER: S-EPMC11538861 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature