Multi-omics characterization of RNA binding proteins reveals disease comorbidities and potential drugs in COVID-19

Pan, Jiwei; Gao, Yueying; Han, Huirui; Pan, Tao; Guo, Jing; Li, Si; Xu, Juan; Li, Yongsheng

doi:10.1016/j.compbiomed.2023.106651

Cited by 1 publication

(1 citation statement)

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“…Researchers have found pioglitazone and lapatinib as potential drugs since pioglitazone decreases the expression of RPS3, eIF4B, and RPS10, while lapatinib decreases the expression of EEF1A1, EIF5A, and RPS10 RBPs 78 . Another study investigated drugs targeting the interacting proteins of SARS-CoV-2-related RBPs and identified Doxorubicin and Topotecan as possible drugs targeting protein interactome of RBPs 79 , providing another way to use RBPs in the treatment of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19

Shi,

Chen,

Pan

et al. 2023

Sci Rep

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The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R2 > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions. These genes are enriched in the immune response pathway and viral life cycle. It has been found that host RNA binding proteins (RBPs) participate in different phases of the SARS-CoV-2 life cycle. We collect 503 RBPs that interact with SARS-CoV-2 RNA concluded from in vitro studies. Combining risk genes from the HGI with RBPs, we identify two COVID-19 risk loci that regulate the expression levels of FUBP1 and RAB2A in the lung. Due to the risk allele, COVID-19 patients show downregulation of FUBP1 and upregulation of RAB2A. Using single-cell RNA sequencing data, we show that FUBP1 and RAB2A are expressed in SARS-CoV-2-infected upper respiratory tract epithelial cells. We further identify NC_000001.11:g.77984833C>A and NC_000008.11:g.60559280T>C as functional variants by surveying allele-specific transcription factor sites and cis-regulatory elements and performing motif analysis. To sum up, our research, which associates human genetics with expression levels of RBPs, identifies FUBP1 and RAB2A as two risk genes for COVID-19 and reveals the anti-viral role of FUBP1 and the pro-viral role of RAB2A in the infection of SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%