Quantum Molecular Resonance attenuates an oxidative stress-induced chimeric transcriptome program in human retinal pigment epithelial cells, preserving RNA structural fidelity

Chimeric and fusion-like transcripts are increasingly recognized as dynamic, non-genomic responses to acute environmental stress. Elevated reactive oxygen species (ROS) compromise RNA Polymerase II (RNAPII) termination and splicing fidelity, generating a potentially proteotoxic burden of structurally aberrant RNAs. However, robust quantification of these stress-induced chimeras in non-tumor perturbation models remains technically challenging. We profiled the structural fidelity of the transcriptome across a large-scale RNA-seq cohort (n=72 samples) centered on Quantum Molecular Resonance (QMR) therapy and oxidative stress (H2O2 400 µM) in ARPE-19 human retinal pigment epithelial cells, across four treatment groups (Control, QMR Rescue, Secretome, QMR+Secretome Rescue) at 8h, 24h, and 72h post-challenge. Using a stringently uniform bioinformatic pipeline (CLC Genomics Workbench v25.0.3, Detect and Refine Fusion Genes v1.6; hg38/Ensembl v113), chimeric events were stratified into three escalating confidence tiers: Tier 1 (PASS), Tier 2 (PASS + in-frame CDS), and Tier 3 (high-confidence: PASS + in-frame + spanning reads > 0). Ubiquitous background chimeras constitutively expressed across all conditions (e.g., NBPF14--NOTCH2, FBXL5--ENSG00000305512, RAB27A--PIGBOS1) were explicitly identified and partitioned from the dynamic, treatment-responsive fraction. Oxidative stress significantly exacerbated the global Chimeric Burden at 72 hours, with mean aggregate read support surging to 575.5 (SD 55.1) in the Control-OX group. QMR Rescue and QMR+Secretome treatment profoundly attenuated this structural derailment (525.5 ± 139.3 and 449.0 ± 33.9, respectively). A robust 25-event QMR-Rescued Signature was derived, mapping OX-induced chimeras to four discrete biological modules: (I) Lipid/Steroidogenic pathway integrity (CTDNEP1--ENSG00000262526, HSD17B7P2--HSD17B7); (II) Extracellular matrix structural integrity (COL7A1--UCN2, COP1-DT--PAPPA2); (III) Nuclear architecture and mitochondrial coupling (COX17--POPDC2); and (IV) Zinc-finger transcriptional networks (ZNF721--ABCA11P, ZNF782--ZNF510). Top events were orthogonally validated by Arriba and STAR-Fusion (93.3% concordance, 14/15 events), and physically confirmed by junction-spanning RT-qPCR and Sanger sequencing. These findings unveil structural transcriptomic fidelity as a third, unprecedented hierarchical layer of QMR-mediated cellular protection—complementing previously described lncRNA-mediated abundance regulation and miRNA-mediated stability control—and establish a rigorous analytical framework for non-oncological chimeric RNA profiling.