Key result
SARS-CoV-2 NSP12 interacts with host splicing factors SLU7, PPIL3, and AKAP8, which regulate viral polymerase activity, pseudovirus entry, and cellular alternative splicing.
Why the study?
The molecular mechanism of the catalytic subunit NSP12 of RdRp involved in pathogenesis remained unclear.
SARS-CoV-2 NSP12 interacts with host splicing factors to regulate viral replication and entry, providing potential new targets for antiviral therapies.
Answers are grounded in this paper and cite their sources.
May guide antiviral targeting of NSP12; leaves open validation in disease models and clinical translation.
Background The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses SARS-CoV-2, SARS-CoV, and MARS-CoV have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. Results In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8), suggesting that the polymerase activity and stability of SARS-CoV-2 RdRp were affected by them to varying degrees. Furthermore, the entry efficacy of SARS-CoV-2 pseudovirus considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. In addition, NSP12 and its homologues from SARS-CoV and MARS-CoV suppressed thealternative splicing (AS) of cellular genes, which were influenced by the three splicing factors. Conclusions Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.
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Yang et al. (2023) studied SARS-CoV-2 infection (in vitro). SARS-CoV-2 NSP12 and host splicing factors (SLU7, PPIL3, AKAP8) vs. Control cells (wild-type or empty vector) was evaluated on Polymerase activity, pseudovirus entry, and alternative splicing. SARS-CoV-2 NSP12 interacts with host splicing factors SLU7, PPIL3, and AKAP8, which regulate viral polymerase activity, pseudovirus entry, and cellular alternative splicing.
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