Alternative Transcribed 3' Isoform of Long Non-coding RNA Inhibits Mouse Retinal Oxidative Stress

The function of the cancer-associated lncRNA during aging is as-of-yet uncharacterized. Here, we show that interacts with Nucleophosmin (NPM) in young mouse brain, and with Lamin A/C, hnRNP C, and KAP1 with age. RNA-seq and RT-qPCR reveal a persistent expression of 2 (the 3'isoform of ) in Δ1 (5'-1.5 kb deletion) mouse retinas and brains at 1/4 level of the full-length , while 1 (the 5'isoform) in Δ2 (deletion of 3'-conserved 5.7 kb) at a much lower level, suggesting an internal promoter driving the 3' isoform. The 1774 and 496 differentially expressed genes in Δ2 and Δ1 brains, respectively, suggest the 3' isoform regulates gene expression and the 5' isoform . Consistently, Δ2 mice show increased age-dependent retinal oxidative stress and corneal opacity, while Δ1 mice show no obvious phenotype. Collectively, this study reveals a physiological function of the lncRNA 3'-isoform during the aging process.