{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:01:47Z","timestamp":1785276107375,"version":"3.55.0"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018817","name":"LUPUS UK","doi-asserted-by":"publisher","award":["R2023AU0131"],"award-info":[{"award-number":["R2023AU0131"]}],"id":[{"id":"10.13039\/501100018817","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Excess neutrophil apoptosis and the release of neutrophil extracellular traps (NETs) in systemic lupus erythematosus (SLE) lead to the accumulation of cell debris and the 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 noncoding 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 noncoding RNAs, 236 piwiRNAs, and 83 tRNA fragments in SLE neutrophils compared to HC (false discovery rate [FDR] adj. P &amp;lt; 0.05). We also identified 78 significant alternative splicing events across 64 genes (FDR adj. P &amp;lt; 0.05, \u0394percent spliced in (PSI) &amp;gt; 0.1 or &amp;lt; \u22120.1). Bioinformatic analysis of miRNA:mRNA DE genes predicted significant activation of autophagy, neutrophil degranulation, interferon alpha\/beta signaling, and apoptosis pathways in SLE neutrophils. Translation and mRNA processing were predicted to be downregulated. microRNAs implicated in NETs production were miR-155-5p, miR-146a-5p, and miR-let-7b-5p (FDR adj. P &amp;lt; 0.05). SNORD89 was identified as a potential promoter of apoptosis in SLE neutrophils, along with alternative splicing of apoptosis genes myeloid cell leukemia-1 (MCL1), caspase-8 (CASP8), and death-associated protein kinase-2 (DAPK2) (FDR adj. P &amp;lt; 0.05). Our study, for the first time, describes dysregulated expression of small noncoding RNAs in SLE neutrophils and proposes noncoding RNA and alternative gene splicing as regulators of neutrophil-driven disease pathology in SLE.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag100","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:49:50Z","timestamp":1784116190000},"source":"Crossref","is-referenced-by-count":0,"title":["A role for noncoding RNAs and alternative splicing in the regulation of neutrophil activation and gene expression in systemic lupus erythematosus"],"prefix":"10.1093","volume":"118","author":[{"given":"Grace","family":"Filbertine","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX ,","place":["United 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Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Haldenby","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, Mersey Bio Building, Crown Street, University of Liverpool , Liverpool L69 7ZB ,","place":["United Kingdom"]},{"name":"Centre for Genomics Research, Shared Research Facilities, University of Liverpool , Mersey Bio Building, Liverpool L69 7ZB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw Batten","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, University of Manchester , Michael Smith Building, Dover Street, Manchester M13 9PL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"McLaren","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Broadgreen Hospital, Liverpool University Hospitals NHS 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