The leader RNA of SARS-CoV-2 sequesters polypyrimidine tract binding protein (PTBP1) and influences pre-mRNA splicing in infected cells

Virology. 2024 Jan 6;592:109986. doi: 10.1016/j.virol.2024.109986. Online ahead of print.ABSTRACTThe large amount of viral RNA produced during infections has the potential to interact with and effectively sequester cellular RNA binding proteins, thereby influencing aspects of post-transcriptional gene regulation in the infected cell. Here we demonstrate that the abundant 5' leader RNA region of SARS-CoV-2 viral RNAs can interact with the cellular polypyrimidine tract binding protein (PTBP1). Interestingly, the effect of a knockdown of PTBP1 protein on cellular gene expression is also mimicked during SARS-CoV-2 infection, suggesting that this protein may be functionally sequestered by viral RNAs. Consistent with this model, the alternative splicing of mRNAs that is normally controlled by PTBP1 is dysregulated during SARS-CoV-2 infection. Collectively, these data suggest that the SARS-CoV-2 leader RNA sequesters the cellular PTBP1 protein during infection, resulting in significant impacts on the RNA biology of the host cell. These alterations in post-transcriptional gene regulation may play a role in SARS-CoV-2 mediated molecular pathogenesis.PMID:38290414 | DOI:10.1016/j.virol.2024.109986

Source: Virology - January 30, 2024 Category: Virology Authors: Noelia H Altina David G Maranon John R Anderson Meghan K Donaldson Suad Elmegerhi Laura A St Clair Rushika Perera Brian J Geiss Jeffrey Wilusz Source Type: research