Nuclear retention is a mechanism whereby RNA transcripts are held in the nucleus to maintain a proper nuclear-to-cytoplasmic balance or as a stockpile for use in responding to stimuli. Many mechanisms are employed to determine whether transcripts are retained or exported to the cytoplasm, though the extent to which tissue- or cell-type, stressors, or disease pathogenesis affect this process remains unclear. As the most biochemically active tissue in the body, the retina must mitigate endogenous and exogenous stressors to maintain cell health and tissue function. Oxidative stress, believed to contribute to the pathogenesis, or progression, of age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs), is produced both internally from biochemical processes, as well as externally from environmental insult. To evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), we performed poly-A RNA sequencing on nuclear and cytoplasmic fractions from induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide, as well as untreated controls. Under normal conditions, the number of mRNA transcripts retained in the nucleus exceeded that found in studies of other tissues. Further, the nuclear-to-cytoplasmic ratio of transcripts is altered following oxidative stress, as is the retention of genes associated with AMD, IRDs, and those important for RPE physiology. These results provide a retention catalog of all expressed mRNA in iPSC-RPE under normal conditions and after exposure to hydrogen peroxide, offering insight into one of the potential roles oxidative stress plays in the progression of visual disorders.

中文翻译：

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氧化应激改变视网膜色素上皮中致病基因的转录本定位

核保留是一种机制，RNA转录物可保持在核内，以维持适当的核-细胞质平衡或作为储备，用于对刺激作出反应。尽管尚不清楚组织或细胞类型，应激源或疾病发病机理影响该过程的程度，但仍采用许多机制来确定转录物是保留还是输出至细胞质。作为体内最具有生物化学活性的组织，视网膜必须缓解内源性和外源性应激源，以维持细胞健康和组织功能。据信，氧化应激是由年龄相关性黄斑变性（AMD）和遗传性视网膜营养不良（IRD）的发病机理或进展引起的，其既是由生化过程内部产生的，也可能是由于环境侵害而产生的。为了评估氧化应激对视网膜色素上皮（RPE）中转录本定位的影响，我们对暴露于氢气的诱导多能干细胞衍生的视网膜色素上皮（iPSC-RPE）细胞的核和细胞质级分进行了poly-A RNA测序过氧化物以及未经处理的对照。在正常条件下，保留在细胞核中的mRNA转录物数量超过了其他组织研究中发现的数量。此外，转录物的核质比在氧化应激后发生改变，与AMD，IRD和对RPE生理学重要的基因相关的基因保留也是如此。这些结果提供了在正常条件下以及暴露于过氧化氢后，iPSC-RPE中所有表达的mRNA的保留目录。