Related Experiment Video
Updated: Sep 12, 2025

Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
Inhibition of coronaviral exonuclease activity by TRIM-mediated SUMOylation
Kannan Balakrishnan1, Surajit Chakraborty1, Cindy Chiang1
1Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL 34987, USA.
Abstract:
Members of the TRIM E3 ligase family are effectors of the host innate or intrinsic defense against various viruses; however, how specific TRIM proteins antagonize coronavirus infection is still largely elusive. Through an RNAi screen targeting 71 human TRIM genes, we identified multiple TRIM proteins with antiviral or proviral activity against SARS-CoV-2. TRIM32 potently restricted SARS-CoV-2 replication in a RING E3 ligase-dependent but interferon-independent manner. Mechanistically, TRIM32 binds to and SUMOylates the 3'-to-5' exoribonuclease (ExoN) of NSP14, which is essential for SARS-CoV-2 replication. TRIM32-mediated NSP14 SUMOylation at K9 and K200 inhibits RNA binding and NSP10 cofactor recruitment, respectively, ultimately suppressing ExoN activity. Our study further revealed that NSP14 SUMOylation by TRIM32 and its antiviral activity are broadly conserved for coronaviruses. These results identify the coronaviral NSP14 protein as a direct target of host restriction via SUMOylation, which may uncover novel ways to therapeutically inhibit coronavirus infections in humans.
Related Concept Videos
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Inhibition of Cdk Activity
Enzyme Inhibition
RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Nuclear Export of mRNA

