Extended Data Fig. 10: Summary schemes of experimental approaches and METTL3 protein structural modeling (related to Fig. 8).
a, Western-blot analyses of indicated proteins in human islets cells treated with DMSO, 1μM thapsigargin, or 2μg/mL tunicamycin for 24h (n = 2 biological independent samples/group). b, Protein quantification of indicated proteins related to (a). c, Western-blot analyses of indicated proteins in EndoC-βH1 cells treated with DMSO, 25μM H2O2, or 25μM H2O2 + 5μM MG132 for 24h (n = 3 independent experiments/group). d, Protein quantification of indicated proteins related to (c). e, Summary scheme of experimental approach to measure METTL3 SNO by LC-MS/MS. f, MS/MS spectra of S-nitrosylated METTL3 peptides and the identification of cysteines C276, C294, C326, and C336 (n = 2 replicates). g, Predicted aligned error related to Fig. 8i–k. The color at position (x, y) indicates AlphaFold’s expected position error at residue x, when the predicted and true structures are aligned on residue y. h, CLUSTAL (1.2.4) multiple sequence alignment of METTL3 in represented species. i, Conceptual model of the role of METTL3 in controlling the OAS innate antiviral immune response by regulating the formation of deleterious dsRNAs and/or controlling viral response. The METTL3 response is decreased by the presence of ER stress and increased ROS levels, resulting from several potential factors such as hyperglycemia, dyslipidemia, genetic, or other environmental mediators such as pollution. Data were expressed as means ± SEM. Statistical analysis was performed by Two-Way ANOVA with Holm-Sidak test in b, and One-Way ANOVA with Holm-Sidak test in d. Source unprocessed gel images and numerical data are available in source data.
