SARS-CoV-2-Induced PAPOLG Contributes to Inflammation Response by Stabilizing NF-κB mRNA

One of the unknowns related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the mechanism underlying the inflammatory response induced by the virus. Poly(A) polymerase gamma (PAPOLG) was previously shown to be upregulated during SARS-CoV-2 infection. The present study explored how PAPOLG affects the inflammatory reaction triggered by SARS-CoV-2. PAPOLG was knocked down or overexpressed in THP-1 macrophages. Target pathways were identified using RNA sequencing and bioinformatics analysis. The levels of PAPOLG, transcriptional regulator nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cytokines TNF-α and IL-6 were measured, along with an assessment of NF-κB mRNA stability. PAPOLG was significantly upregulated in SARS-CoV-2-infected THP-1 macrophages. Genes subjected to alternative polyadenylation were enriched in immune pathways, and NF-κB emerged as a key regulator. Knockdown of PAPOLG promoted NF-κB mRNA degradation, while decreasing the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL6). Conversely, overexpression of PAPOLG stabilized NF-κB mRNA and enhanced TNF-α and IL-6 expression. PAPOLG contributes to the inflammatory response in SARS-CoV-2-infected macrophages by stabilizing NF-κB mRNA. Thus, PAPOLG may be targeted to control COVID-19-related inflammation.