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Sci Rep ; 12(1): 364, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1617003

ABSTRACT

RNA-binding proteins (RBPs) interact with and determine the fate of many cellular RNAs directing numerous essential roles in cellular physiology. Nuclear Factor 90 (NF90) is an RBP encoded by the interleukin enhancer-binding factor 3 (ILF3) gene that has been found to influence RNA metabolism at several levels, including pre-RNA splicing, mRNA turnover, and translation. To systematically identify the RNAs that interact with NF90, we carried out iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) analysis in the human embryonic fibroblast cell line HEK-293. Interestingly, many of the identified RNAs encoded proteins involved in the response to viral infection and RNA metabolism. We validated a subset of targets and investigated the impact of NF90 on their expression levels. Two of the top targets, IRF3 and IRF9 mRNAs, encode the proteins IRF3 and IRF9, crucial regulators of the interferon pathway involved in the SARS-CoV-2 immune response. Our results support a role for NF90 in modulating key genes implicated in the immune response and offer insight into the immunological response to the SARS-CoV-2 infection.


Subject(s)
COVID-19/metabolism , Immunoprecipitation/methods , Nuclear Factor 90 Proteins/metabolism , RNA-Binding Proteins/metabolism , RNA/metabolism , SARS-CoV-2/metabolism , COVID-19/virology , Cells, Cultured , HEK293 Cells , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics , Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism , Nuclear Factor 90 Proteins/genetics , Protein Binding , RNA/genetics , RNA Interference , RNA Stability , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Seq/methods , SARS-CoV-2/genetics , SARS-CoV-2/physiology
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