Nitric oxide drives proteomic diversity through alternative splicing
Year: 2026
Type: article
Abstract: Redox signaling by nitric oxide (NO) is estimated to control a 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 disease 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.
Source: Molecular Cell
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: University of Washington, Case Western Reserve University, National Institutes of Health, University of California, San Diego, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences
OpenAlex ID: W7162007371