Enhanced Transcriptomic Resilience following Increased Alternative Splicing and Differential Isoform Production between Air Pollution Conurbations

Adverse health outcomes caused by ambient particulate matter (PM) pollution occur in a progressive process, with neutrophils eliciting inflammation or pathogenesis. We investigated the toxico-transcriptomic mechanisms of PM real-life settings comparing healthy residents living Beijing and Chengde, opposing ends well-recognised air (AP) corridor China. recruits (BRs) uniquely expressed ~12,000 alternative splicing (AS)-derived transcripts, largely elevating proportion transcripts significantly correlated concentration. BRs PM-associated isoforms (PMAIs) PFKFB3 LDHA, encoding enzymes responsible for stimulating maintaining glycolysis. PMAIs featured different COOH-terminals, targeting to sub-cellular functional compartments LDHA have longer 3′UTRs relative those Chengde (CRs), allowing glycolysis maintenance enhancing mRNA stability translational efficiency. were directly regulated HIF-1A HIF-1B isoforms. more non-functional Fas isoforms, resultant reduction intact is expected inhibit transmission apoptotic signals prolong neutrophil lifespan. both membrane-bound soluble IL-6R instead only one CRs. The presence suggested higher migration capacity BRs. downregulated Chronic Obstructive Pulmonary Disease patients compared BRs, implying HIF-1 mediated defective may mediate dysfunction. could explain large variances phenotypes, highlighting their potential application as biomarkers therapeutic targets PM-induced diseases, which remain poorly elucidated.