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J Biol Chem
. 2024 Sep 27:107834.
doi: 10.1016/j.jbc.2024.107834. Online ahead of print. Structural basis for the participation of the SARS-CoV-2 nucleocapsid protein in the template switch mechanism and genomic RNA reorganization
Peter R Bezerra 1 , Fabio C L Almeida 2
Affiliations
The COVID-19 pandemic has resulted in a significant toll of deaths worldwide, exceeding seven million individuals, prompting intensive research efforts aimed at elucidating the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 infection. Despite the rapid development of effective vaccines and therapeutic interventions, COVID-19 remains a threat to humans due to the emergence of novel variants and largely unknown long-term consequences. Among the viral proteins, the nucleocapsid protein (N) stands out as the most conserved and abundant, playing the primary role in nucleocapsid assembly and genome packaging. The N protein is promiscuous for the recognition of RNA, yet it can perform specific functions. Here, we discuss the structural basis of specificity, which is directly linked to its regulatory role. Notably, the RNA chaperone activity of N is central to its multiple roles throughout the viral life cycle. This activity encompasses double-stranded RNA (dsRNA) annealing and melting and facilitates template switching, enabling discontinuous transcription. N also promotes the formation of membraneless compartments through liquid‒liquid phase separation (LLPS), thereby facilitating the congregation of the replication and transcription complex (RTC). Considering the information available regarding the catalytic activities and binding signatures of the N protein‒RNA interaction, this review focuses on the regulatory role of the SARS-CoV‒2 N protein. We emphasize the participation of the N protein in discontinuous transcription, template switching, and RNA chaperone activity, including double-stranded RNA melting and annealing activities.
Keywords: Nucleocapsid protein; RNA chaperone; RNA-binding; SARS-CoV-2; coronavirus.
. 2024 Sep 27:107834.
doi: 10.1016/j.jbc.2024.107834. Online ahead of print. Structural basis for the participation of the SARS-CoV-2 nucleocapsid protein in the template switch mechanism and genomic RNA reorganization
Peter R Bezerra 1 , Fabio C L Almeida 2
Affiliations
- PMID: 39343000
- DOI: 10.1016/j.jbc.2024.107834
The COVID-19 pandemic has resulted in a significant toll of deaths worldwide, exceeding seven million individuals, prompting intensive research efforts aimed at elucidating the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 infection. Despite the rapid development of effective vaccines and therapeutic interventions, COVID-19 remains a threat to humans due to the emergence of novel variants and largely unknown long-term consequences. Among the viral proteins, the nucleocapsid protein (N) stands out as the most conserved and abundant, playing the primary role in nucleocapsid assembly and genome packaging. The N protein is promiscuous for the recognition of RNA, yet it can perform specific functions. Here, we discuss the structural basis of specificity, which is directly linked to its regulatory role. Notably, the RNA chaperone activity of N is central to its multiple roles throughout the viral life cycle. This activity encompasses double-stranded RNA (dsRNA) annealing and melting and facilitates template switching, enabling discontinuous transcription. N also promotes the formation of membraneless compartments through liquid‒liquid phase separation (LLPS), thereby facilitating the congregation of the replication and transcription complex (RTC). Considering the information available regarding the catalytic activities and binding signatures of the N protein‒RNA interaction, this review focuses on the regulatory role of the SARS-CoV‒2 N protein. We emphasize the participation of the N protein in discontinuous transcription, template switching, and RNA chaperone activity, including double-stranded RNA melting and annealing activities.
Keywords: Nucleocapsid protein; RNA chaperone; RNA-binding; SARS-CoV-2; coronavirus.