Ghanam Amr R, Ke Shengwei, Wang Shujuan, Elgendy Ramy, Xie Chenyao, Wang Siqi, Zhang Ran, Wei Min, Liu Weiguang, Cao Jun, Zhang Yan, Zhang Zhi, Xue Tian, Zheng Yong, Song Xiaoyuan
Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China.
Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
iScience. 2022 Dec 5;26(1):105740. doi: 10.1016/j.isci.2022.105740. eCollection 2023 Jan 20.
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.
癌症相关长链非编码RNA在衰老过程中的功能尚未明确。在此，我们发现其在年轻小鼠大脑中与核磷蛋白（NPM）相互作用，随着年龄增长则与核纤层蛋白A/C、异质性核糖核蛋白C（hnRNP C）和KRAB相关蛋白1（KAP1）相互作用。RNA测序和逆转录定量聚合酶链反应（RT-qPCR）显示，在Δ1（5'-1.5 kb缺失）小鼠的视网膜和大脑中，2（的3'异构体）持续表达，其水平为全长的1/4，而在Δ2（3'-保守的5.7 kb缺失）中1（的5'异构体）的表达水平则低得多，这表明存在一个内部启动子驱动3'异构体的表达。分别在Δ2和Δ1大脑中差异表达的1774个和496个基因表明，3'异构体调节基因表达，而5'异构体则不然。一致的是，Δ2小鼠表现出年龄依赖性视网膜氧化应激增加和角膜混浊，而Δ1小鼠没有明显的表型。总的来说，这项研究揭示了长链非编码RNA 3'异构体在衰老过程中的生理功能。
