Genome-wide analysis of RNA-binding protein co-expression with alternative splicing events in acute respiratory distress syndrome following hematopoietic stem cell transplantation

Abstract

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing severe acute respiratory distress syndrome (ARDS), which is characterized by peripheral bilateral patchy lung involvement. The regulatory network of RNA-binding protein (RBP)-alternative splicing (AS) in ARDS following HSCT has not been investigated. We hypothesize that RBP-AS plays a regulatory role during HSCT-ARDS. The published ARDS transcriptome data after HSCT (GSE84439) were downloaded, and the transcriptome data of 13 mRNAs were obtained by sequencing the peripheral blood of 5 HSCT-ARDS patients and 8 ARDS patients through high-throughput sequencing technology. Systematic analysis of downloaded data was performed to obtain differentially expressed RBPs, and the differentially alternative spliced pre-mRNAs in HSCT-ARDS and control groups were used to explore the global gene RBP-AS regulatory network. A total of 1769 differentially expressed genes and 4714 regulated alternative splicing events were identified in peripheral blood from HSCT-ARDS, of which 254 genes had both differential expression and differential AS. In addition, 128 RBPs were identified, of which HDGF, PCBP2, RIOK3, CISD2, and TRIM21, DDX58, MOV10 showed significantly increased or decreased expression in the HSCT-ARDS. RBPs with decreased expression had antiviral activity, while those with increased expression were involved in ROS, fibrosis, and negative viral resistance. The RBP-RASE-RASG regulatory network is constructed. It is related to the dysregulation of antiviral immunomodulation, imbalance in ROS homeostasis and pro-pulmonary fibrosis, which are involved in the development of HSCT-ARDS.