RNA-dependent RNA polymerase of SARS-CoV-2 regulate host mRNA translation efficiency by hijacking eEF1A factors.

Publication date: Sep 04, 2023

The RNA-dependent RNA polymerase (NSP12) of COVID-19 plays a significant role in the viral infection process, which promotes viral RNA replication by cooperating with NSP7 and NSP8, but little is known about its regulation on the function of host cells. We firstly found that overexpression of NSP12 had little effect on host mRNAs transcription. Using iCLIP technology, we found that NSP12 can bind a series of host RNAs with the conserved binding motif G(C/A/G)(U/G/A)UAG, especially ribosomal RNA. We found that NSP12 could directly bind to eEF1A factor via the NIRAN domain of NSP12 and N-terminal domain of eEF1A. NSP12 colocalized with eEF1A to inhibit type I interferon expression upon virus infection. In order to prove that NSP12 regulates the translation level of host cells, we found that NSP12 significantly affected the translation efficiency of many host mRNAs (such as ISG15, NF-_705B2, ILK and SERPINI2) via ribosome profiling experiment, and the genes with significant upregulation in translation efficiency were mainly enriched in positive regulation of ubiquitin-dependent proteasomal process and NIK/NF-_705B signaling pathway (such as NF-_705B2, ILK), and negative regulation of type I interferon production, protein level of these genes were further confirmed in HEK293T and Calu3 cells upon NSP12 overexpression. These results indicate that NSP12 of SARS-CoV-2 can hijack the eEF1A factor to regulate translation efficiency of host mRNAs, which provides a new idea for us to evaluate the impact of SARS-CoV2 virus on the host and study the potential drug targets.

Concepts Keywords
Hek293t COVID-19
Hijacking eEF1A
Overexpression iCLIP
Ribosomal Ribosome profiling


Type Source Name
pathway KEGG RNA polymerase
disease IDO host
pathway REACTOME Translation
disease VO efficiency
disease MESH COVID-19
disease MESH viral infection
disease IDO process
pathway KEGG Ribosome

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