Fig 2: PRMT7 targets RAP1A expression through histone methylation.a Western blot analysis of RAP1A/RAP1B expression in Prmt7+/+ and Prmt7null MH-S cells (repeated twice). b mRNA expression level of Rap1a and Rap1b determined by qPCR in Prmt7+/+ and Prmt7null MH-S macrophage cells (n = 4 replicates per cell line). c–f ATAC-Seq analysis of Prmt7+/+ v Prmt7null MH-S cells. c ATAC-seq signal enrichment peaks around the transcription start site (TSS) of the Rap1a gene in Prmt7+/+ and Prmt7null MH-S cells and difference in peak height across the two lines. d Heat map of tag distributions across TSSs for Prmt7+/+ and Prmt7null MH-S cells. e Peak correlation scatter plot. f Pie chart showing the genomic distribution of accessible regions in Prmt7+/+ and Prmt7null MH-S cells. g Schematic representation of the location of the Rap1a regions targeted for qPCR following ChIP, plus H3K4me1 and H3K27a enrichment in BMDM (from UCSC genome browser Track accessions: wgEncodeEM002658 and wgEncodeEM002657). h Enrichment of H3R2 mono and dimethylation at Rap1a regions in Prmt7+/+ and Prmt7null MH-S by qPCR following ChIP (n = 2 per cell line). i Western blot analysis of mono and dimethylation of H3R2 in Prmt7+/+ and Prmt7null MH-S cells (repeated twice). j Dot blot depicting Rap1a expression (log-transformed, normalized UMI counts) and percentage of cells positive for Rap1a in monocytes from mouse lung single-cell RNA-seq data following exposure to FA (n = 3) and CS for 2 (n = 5) and 4 months (n = 5). k mRNA expression levels of RAP1A determined by qPCR in the monocytes of smokers (n = 10) and non-smokers (n = 11) isolated from the peripheral blood. l MFI of ITGAL and ITGAM surface expression as determined by flow cytometry in Prmt7+/+ MH-S cells incubated with 20 μM GGTI (RAP1 inhibitor) for 2 h and analysed 6 h later (n = 2, repeated three times). m Western blot analysis of phosphorylated ERK in WT MH-S cells pretreated with the RAP1 inhibitor GGTI (20 μM) for 2 h and incubated for 15 min with 1 μg/ml LPS. Quantification relative to actin shown (repeated two times). Data shown mean ± SD, P values shown in charts determined by unpaired two-tailed Student’s t-test (b, h, k, l), one-way ANOVA Bonferroni’s multiple comparisons test (m). Source data are provided as a Source Data file.

Fig 3: Propofol elevated miR-486-5p to enhance DDP-sensitivity in DDP-resistant NSCLC cells via RAP1-NF-κB axis. The A549/DDP and SKMES/DDP cells were intervened with miR-486-5p inhibitor and siRNA-RAP1, and intervened with 10 μg/mL of propofol and 40 μM of DDP for 24 h. a The transfection efficiency was tested by qRT-PCR. b Cell viability at 48 h was evaluated through CCK8 assay. c The colony formation ability was measured by Giemsa staining. d The apoptosis was detected by flow cytometry. e The A549/DDP and SKMES/DDP cells were treated with different concentrations of DDP (0, 20, 40, 60, 80, 100 μM), and then cell viability was detected by CCK-8 assay. f The IC50 value was calculated according to the dose survival curve. *P < 0.05. NC, negative control. Ppf, high concentration of propofol. miR in, miR-486-5p inhibitor. si-RAP1, siRNA-RAP1

Fig 4: PRMT7 expression is increased in COPD lungs and localized to macrophages.a Heat map of the most significantly enriched gene lists in the lungs of COPD patients following gene set enrichment analysis (GSEA) of the GO molecular function set on publicly available array data from lung tissue (GSE76925) of healthy smokers (n = 40) v COPD patients (n = 111). Nominal P value generated by the GSEA software of the enrichment score relative to the null distribution92 shown. b Expression of genes involved in N-methyltransferase activity in COPD patients relative to healthy smokers taken from GSE76925, relative fold change, and P value calculated using the GEO2R interactive web tool running limma R. PRMT genes highlighted in red. c, d Expression of PRMT7, in the lungs of healthy smokers and COPD patients, individuals are shown, expression relative to healthy smokers, taken from GSE76925 (n = 40 smokers and n = 111 COPD patients) (c) and GSE27597 (n = 16 smokers and n = 48 COPD patients) (d). e qPCR analysis of PRMT7 and TNF expression in human lung core biopsies from healthy controls (n = 8) and COPD patients (n = 18) relative to controls. f Western blot analysis of PRMT7 expression in lung core biopsies from healthy (n = 17) and COPD patients (n = 23), normalized to β-actin and shown relative to controls. g Representative images of immunofluorescence analysis for PRMT7 (Red) and the macrophage marker Galectin 3 (Green) in sections from core biopsies of healthy and COPD human lung (n = 4, scale bar 20 μm) and sections from filtered air (FA) and cigarette smoke (CS) mouse lung (n = 5, scale bar 25 μm). h Quantification of double-positive cells from (g). i, j mRNA expression levels of PRMT7 determined by qPCR in human monocytes isolated from blood of non-smokers (n = 7) vs smokers (n = 10) (i) and circulating monocytes (n = 4 for FA and CS) (i) and alveolar macrophages (n = 4 for FA and n = 3 for CS) (j) from B6 mice exposed to FA or CS for 3 days, relative to controls. k–m scRNA-Seq (Drop-Seq) analysis on the lungs of mice following exposure to FA (n = 3) and CS for 2 (n = 5) and 4 months (n = 5). AM alveolar macrophages, CS-ind MØ CS-induced macrophages, IM interstitial macrophages, cMono classical monocytes. k Dot blot depicting Prmt7 expression (log-transformed, normalized UMI counts) and percentage of cells positive for Prmt7 in the myeloid cell compartment. l RNA velocity analysis of the myeloid compartment. (1) AM; (2) CS-ind MØ; (3) Lyve1 + /Cd163 + IM; (4) Lyve1−/Cd163− IM; (5) Prg4 + IM; (6) Ly6c2 + cMono; (7) Ly6c2- non-cMono; (8) Cd103 + /Clec9a + cDC; (9) Cd209 + /Cd11b + cDC; (10) Fscn1 + DC. m Fate probability mapping towards the CS-ind MØ population utilizing CellRank. n Heat map of gene expressions of PRMT6/7, RAP1A, and ALOX5 in monocyte-like macrophages obtained from scRNA-Seq data of bronchoalveolar lavage from COPD patients (n = 9) and healthy controls (n = 6). Mean gene expression per donor is shown as a z-transformed value (across all donors). Data shown mean ± SD and individual patients or mice (c–f and h–j), P values shown in charts determined by two-tailed Mann–Whitney test (c–f), unpaired two-tailed Student’s t-test (h–j). Source data are provided as a Source Data file.