Re-Analysis of GSE261505 Human Embryonic Kidney 293Cells Treated with siPABPN1 Knockdown

Abstract

The GSE261505 study examined how knocking down the nuclear polyadenylationbinding protein PABPN1alters transcription in HEK293 cells, a factor implicated in RNA maturation and neuromuscular disease. To ex-plore the regulatory networks disrupted by PABPN1 loss, we reanalyzed the data with a concise bioinformaticspipeline: counts and metadata were retrieved from ARCHS4, filtered for proteincoding genes, and differentialexpression was performed with limmavoom to generate up and downregulated gene sets. Enrichment inEnrichr (GO, KEGG, ChEA, KOMP2) and perturbation mapping with PerturbSeqr identified genes and drugs thatmimic or reverse the signature. Upregulated genes clustered in neuronal pathways such as neurotransmitterloading into synaptic vesicles and aminoacid biosynthesis, while downregulated genes were enriched forheatacclimation and nucleotidesynthesis processes. The transcription factor BP1 appeared in both ChEA lists,indicating a dual role. PerturbSeqr revealed that the signature is best mimicked by lossoffunction perturba-tions of chromatin remodelers and tumor suppressors (PTEN, EZH2, YAP1) and reversed by cellcycle activators(CCND1, TP53). These findings suggest that PABPN1 depletion reprograms transcription toward neuronal andmetabolic states while suppressing stressresponse pathways, offering insights into its pathological effects.