Mapping the Regulatory Programs of RNA Binding Protein Regulators in Rheumatoid Arthritis: Data from Single-Cell Transcriptome Analysis

Abstract

Abstract Background RNA binding proteins (RBPs), especially cell-specific RBPs are involved in critical processes such as alternative splicing of messenger RNAs and translational control, leading to the expression of cell-specific functional proteins. However, the expression pattern of RBPs in different cells of rheumatoid arthritis and their associated aberrant regulation remain largely unexplored.Methods We collected 2141 RNA binding protein genes (RBPs) from literature and identified cell populations present in rheumatoid arthritis and osteoarthritis control samples using single-cell data. We compared the changes in the relative proportions of cell classes between them and analyzed RBP expression patterns specific to different cell types. We investigated fibroblast cell populations and their cellular communication with different immune cells. Additionally, we used bulk RNA-seq data from rheumatoid arthritis and osteoarthritis samples to identify highly conserved variable splicing events and established a co-variation network of RBPs and these splicing events.Results We observed a greater number of down-regulated RBPs in each cell type, except for fibroblasts, endothelial cells, and macrophages, where the number of up-regulated genes was much higher. In fibroblasts from RA and OA patients, we identified 105 upregulated RBPs and 133 downregulated RBPs. These RBPs were co-expressed with genes enriched in various functional pathways, including extracellular matrix organization, cell adhesion, collagen fibril organization, and cytokine signaling. Cellular communication analysis demonstrated enhanced signaling pathways, like CXCL12-CXCR4, between fibroblasts and macrophages in RA. We identified a total of 715 differentially variable splicing events in our study, and alternative 5' and 3' splicing were the most prevalent. Some RBPs, such as MBNL2 in endothelial cells and U2AF1, SF3B6, and SF3B14 in fibroblast cells, may play a role in the pathogenesis of RA through splicing regulation.Conclusion In this study, we analyzed single-cell datasets to identify the inherent characteristics and abnormal expression patterns of RBPs in different cell types of patients with RA. Our findings revealed that certain cell-specific RBPs were associated with inflammatory signaling pathways and splicing regulation in RA. These findings suggest that the dysregulation of RBPs may contribute to the development of RA and highlight potential pathways for therapeutic interventions.