A role for non-coding RNAs and alternative splicing in the regulation of neutrophil activation and gene expression in systemic lupus erythematosus

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ID: 321338
2026
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Abstract
Abstract Excess neutrophil apoptosis and the release of neutrophil extracellular traps (NETs) in systemic lupus erythematosus (SLE) leads to accumulation of cell debris and production of auto-antibodies targeting nuclear proteins and DNA. SLE neutrophil activation is regulated by changes in gene expression, notably expression of type-I interferon-response genes and genes coding for granule proteins. This observational study measured both mRNA and small non-coding RNAs in SLE (n = 11) and healthy control (HC, n = 10) ultra-pure blood neutrophils to identify changes in expression that are involved in regulating neutrophil phenotype. Using RNAseq, we identified significant differential expression (DE) of 69 microRNAs, 63 other small non-coding RNAs, 236 piwiRNAs and 83 tRNA fragments in SLE neutrophils compared to HC (false discovery rate (FDR) adj. p < 0.05). We also identified 78 significant alternative splicing events across 64 genes (FDR adj. p < 0.05, Δpercent spliced in (PSI) > 0.1 or < -0.1). Bioinformatic analysis of miRNA:mRNA DE genes predicted significant activation of autophagy, neutrophil degranulation, interferon alpha/beta signalling, and apoptosis pathways in SLE neutrophils. Translation and mRNA processing were predicted to be down-regulated. microRNAs implicated in NETs production were miR-155-5p, miR-146a-5p and miR-let-7b-5p (FDR adj. p < 0.05). SNORD89 was identified as a potential promoter of apoptosis in SLE neutrophils, along with alternative splicing of apoptosis genes myeloid cell leukaemia-1 (MCL1), caspase-8 (CASP8) and death-associated protein kinase-2 (DAPK2) (FDR adj. p < 0.05). Our study describes for the first time, dysregulated expression of small non-coding RNAs in SLE neutrophils and proposes non-coding RNA and alternative gene splicing as regulators of neutrophil-driven disease pathology in SLE.
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openalex_W7168706107 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors
Journal journal of leukocyte biology
Year 2026
DOI
10.1093/jleuko/qiag100
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