GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE286nnn/GSE286543/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286543GEOGSEfalseNitric oxide drives proteomic diversity through alternative splicing [CLIP-Seq]Redox signaling by nitric oxide (NO) is estimated to control the large part of the global proteome via S-nitrosylation (SNO-modification). Here we report that RNA-binding proteins (RBPs) represent the most significantly enriched class of S-nitrosylation targets, with broad coverage of spliceosomal factors. We demonstrate that NO regulates alternative splicing (AS) and that S-nitrosylation of PTBP1, a central regulator of AS, can massively shift and contextually alter gene expression, while further enriching the transcriptome for SNO sites. PTBP1 S-nitrosylation changes RNA-binding domain conformation, RNA motif recognition, protein–RNA and protein–protein interactions, and intracellular trafficking to impact pathways for viral infection and neurodegeneration. Levels of SNO-PTBP1 are reduced in mouse and human Alzheimer’s brains and correlate with adverse clinical outcomes. Overall, SNO-RBPs are characterized by conservation across diverse lineages and SNO sites and provide a blueprint for redox regulation of both transcriptome and proteome in physiology and disease.2026/05/21GSE286543GSM8729057GSM8729068GSM8729056GSM8729067GSM8729066GSM8729055GSM8729065GSM8729059GSM8729069GSM8729058GSM8729060GSM8729070GSM8729064GSM8729063GSM8729062GSM872906121697286543Homo sapiens[42167237]