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Preparation of Viral DNA from Nucleocapsids

Preparation of Viral DNA from Nucleocapsids

Published on: August 16, 2011

Nucleocapsid protein captures DDX5 and RNMT facilitating viral RNA synthesis and viral protein translation for

Yuchang Liu¹, Ning Kong^1,2, Xinyu Yang¹

¹Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, Shanghai, China.

|January 26, 2026

Abstract:

Coronaviruses (CoVs) hijack host RNA-binding proteins (RBPs) to facilitate their replication, but the viral proteins and host RBDs that participate in the synthesis of viral RNA and protein are unclear. In this study, we revealed that DEAD-box helicase (DDX5) and staphylococcal nuclease domain-containing protein (SND1) facilitate viral RNA synthesis and that RNA guanine-7 methyltransferase (RNMT) enhances viral protein translation to promote viral replication via coronaviral subgenomic RNA-protein interactomes. DDX5 and SND1 positively regulate PEDV replication by promoting viral RNA synthesis via the binding of DDX5 to positive-sense viral RNA, whereas SND1 specifically detects negative-sense viral RNA. The interaction of DDX5/SND1 and N/nsp9/nsp12 promotes the formation of replication-transcription complexes for viral RNA synthesis to facilitate viral replication. We found that RNMT captures the host protein translation system to cyclize viral mRNA to assist in viral protein translation to promote viral replication. We also found that DDX5 broadly interacts with the N protein of CoVs and promotes the RNA synthesis of bovine coronavirus and porcine delta-coronavirus to promote viral replication. These results indicate that CoVs use host proteins to assist in the synthesis of viral RNA and protein to facilitate viral replication.

Importance:

The synthesis of viral RNA and proteins is a crucial process in the life cycle of CoVs. Our observations indicate that DDX5 and SND1 facilitate the assembly of viral replication-transcription complexes and enhance viral RNA synthesis, with DDX5 binding to positive-sense RNA and SND1 binding to negative-sense RNA. Meanwhile, RNMT promotes viral protein translation by hijacking the host translation machinery and mediating the circularization of viral mRNA. These findings offer new insights into the mechanisms through which coronaviruses exploit both viral and host proteins to synthesize viral RNA and proteins.

Insights

Coronaviruses (CoVs) utilize host proteins DEAD-box helicase (DDX5) and staphylococcal nuclease domain-containing protein (SND1) for viral RNA synthesis. RNA guanine-7 methyltransferase (RNMT) enhances viral protein translation, promoting CoV replication.

Area of Science:

Virology
Molecular Biology
Biochemistry

Background:

Coronaviruses (CoVs) rely on host RNA-binding proteins (RBPs) for replication.
The specific viral and host factors involved in viral RNA and protein synthesis remain incompletely understood.

Purpose of the Study:

To elucidate the roles of host RBPs in coronavirus replication.
To identify host proteins that facilitate viral RNA synthesis and protein translation.

Main Methods:

Investigated protein-protein interactions between viral components and host RBPs.
Analyzed the impact of host proteins DDX5, SND1, and RNMT on viral RNA synthesis and protein translation.
Examined the binding of DDX5 and SND1 to different forms of viral RNA.

Main Results:

DDX5 and SND1 were found to promote viral RNA synthesis by interacting with viral proteins (N, nsp9, nsp12) and forming replication-transcription complexes.
DDX5 binds to positive-sense viral RNA, while SND1 detects negative-sense viral RNA.
RNMT enhances viral protein translation by hijacking host translation machinery and circularizing viral mRNA.
DDX5 broadly interacts with the CoV N protein, promoting RNA synthesis in other coronaviruses.

Conclusions:

CoVs exploit host proteins DDX5, SND1, and RNMT to facilitate viral RNA and protein synthesis, crucial for replication.
These host factors play distinct roles in RNA synthesis and protein translation, highlighting complex viral-host interactions.

Read full analysis

Keywords:

RNA synthesis RNA-binding proteins coronaviruses protein translation virus-host interaction

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