An N-Terminal Acidic Patch Underlies Differential Inhibition of mRNA Nuclear Export by Human Coronavirus Nsp1 Proteins.
7 affiliations
- 1Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
- 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
- 3University of Chinese Academy of Sciences, Beijing 100049, China.
- 4Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200437, China.
- 5Department of Respiratory and Critical Care Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
- 6Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
- 7Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related human coronaviruses (hCoVs) regulate host gene expression to facilitate viral replication and evade innate immunity. SARS-CoV-2 nonstructural protein 1 (Nsp1) suppresses host gene expression in part by inhibiting cellular mRNA nuclear export through targeting the mRNA export factor NXF1. However, whether this mechanism is conserved among Nsp1 proteins from diverse hCoVs remains unknown. Here, we demonstrate that Nsp1 proteins from SARS-CoV, SARS-CoV-2, and MERS-CoV, but not those from endemic hCoVs, induce pronounced nuclear accumulation of host poly(A) RNA without altering global transcript levels. Nsp1 proteins from these highly pathogenic hCoVs directly interact with NXF1, whereas endemic hCoV Nsp1 proteins show little or no detectable NXF1 interaction. Structural modeling and mutagenesis identify a conserved N-terminal acidic patch in Nsp1 that contacts the basic surface of the NXF1 RNA recognition motif. Disruption of this interface abolishes the Nsp1-NXF1 interaction and restores host mRNA export while preserving NXF1 interactions with core mRNA export factors. Together, our findings define a conserved structural mechanism by which highly pathogenic hCoV Nsp1 targets NXF1 to inhibit host mRNA export and provide a potential framework for broad-spectrum antiviral intervention.
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BibTeX
@article{wang2026nterminal,
title = {{An N-Terminal Acidic Patch Underlies Differential Inhibition of mRNA Nuclear Export by Human Coronavirus Nsp1 Proteins.}},
author = {Fei Wang and Baoyin Su and Ziyan Huang and Ziyun Cheng and Chunhui Chang and Yunjiao Zhang and Leer Shen and Ziyue Li and Jing Zhang and Xiaohua Chen and Jiaming Lan and Yaming Jiu and Xun Chen and Juan Li and Chengyuan Wang and Ke Zhang},
journal = {Viruses},
year = {2026},
month = oct,
doi = {10.3390/v18101157},
url = {https://europepmc.org/article/MED/42944076},
note = {CC BY},
}
RIS
TY - JOUR
TI - An N-Terminal Acidic Patch Underlies Differential Inhibition of mRNA Nuclear Export by Human Coronavirus Nsp1 Proteins.
AU - Fei Wang
AU - Baoyin Su
AU - Ziyan Huang
AU - Ziyun Cheng
AU - Chunhui Chang
AU - Yunjiao Zhang
AU - Leer Shen
AU - Ziyue Li
AU - Jing Zhang
AU - Xiaohua Chen
AU - Jiaming Lan
AU - Yaming Jiu
AU - Xun Chen
AU - Juan Li
AU - Chengyuan Wang
AU - Ke Zhang
PY - 2026
DA - 2026/10/18
JO - Viruses
DO - 10.3390/v18101157
UR - https://europepmc.org/article/MED/42944076
AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related human coronaviruses (hCoVs) regulate host gene expression to facilitate viral replication and evade innate immunity. SARS-CoV-2 nonstructural protein 1 (Nsp1) suppresses host gene expression in part by inhibiting cellular mRNA nuclear export through targeting the mRNA export factor NXF1. However, whether this mechanism is conserved among Nsp1 proteins from diverse hCoVs remains unknown. Here, we demonstrate that Nsp1 proteins from SARS-CoV, SARS-CoV-2, and MERS-CoV, but not those from endemic hCoVs, induce pronounced nuclear accumulation of host poly(A) RNA without altering global transcript levels. Nsp1 proteins from these highly pathogenic hCoVs directly interact with NXF1, whereas endemic hCoV Nsp1 proteins show little or no detectable NXF1 interaction. Structural modeling and mutagenesis identify a conserved N-terminal acidic patch in Nsp1 that contacts the basic surface of the NXF1 RNA recognition motif. Disruption of this interface abolishes the Nsp1-NXF1 interaction and restores host mRNA export while preserving NXF1 interactions with core mRNA export factors. Together, our findings define a conserved structural mechanism by which highly pathogenic hCoV Nsp1 targets NXF1 to inhibit host mRNA export and provide a potential framework for broad-spectrum antiviral intervention.
SN - 1999-4915
ER -