The NF-κB isoform p65 iso5 is associated with distinct transcriptional programs and signaling pathways.

Recent evidence indicates that alternative p65 isoforms may diversify NF-κB signaling, but their functions remain largely unexplored. We previously identified a novel splice variant, p65 iso5, which contains an additional upstream exon and displays distinct molecular properties, including the ability to interact with dexamethasone in a glucocorticoid receptor-dependent manner.

Here, we define the transcriptional programs regulated by p65 iso5 using RNA-seq analysis of HeLa cells expressing either p65 iso5 or canonical p65, with or without dexamethasone treatment. Under basal conditions, p65 iso5 expression was associated with reduced expression of genes involved in type I interferon and antiviral pathways, together with increased expression of genes involved in translation, ribosome biogenesis, and metabolic activity.