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

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.