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Virology . Control of nuclear localization of the nucleocapsid protein of SARS-CoV-2

tetano

Editor, Senior Moderator
Virology


. 2024 Sep 8:600:110232.
doi: 10.1016/j.virol.2024.110232. Online ahead of print. Control of nuclear localization of the nucleocapsid protein of SARS-CoV-2

Mengrui Wang[SUP] 1 [/SUP], Maria Valadez-Ingersoll[SUP] 1 [/SUP], Thomas D Gilmore[SUP] 2 [/SUP]



Affiliations
Abstract

The nucleocapsid (N) protein of coronaviruses is a structural protein that binds viral RNA for assembly into the mature virion, a process that occurs in the cytoplasm. Several coronavirus N proteins also localize to the nucleus. Herein, we identify that two sequences (NLSs) are required for nuclear localization of the SARS-CoV-2 N protein. Deletion or mutation of these two sequences creates an N protein that does not localize to the nucleus in HEK293T cells. Overexpression of both wild-type and NLS-mutated N proteins dysregulate a largely overlapping set of mRNAs in HEK293T cells, suggesting that these N proteins do not have direct nuclear effects on transcription. Consistent with that hypothesis, both N proteins induce nuclear localization of NF-κB p65 and dysregulate a set of previously identified NF-κB-dependent genes. The effects of N on nuclear properties are proposed to alter host cell functions that contribute to viral pathogenesis or replication.

Keywords: Coronavirus; Gene expression; NF-kappaB; Nuclear localization; Nucleocapsid protein; SARS-CoV-2.

 
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