Flores Carlos C, Pasetto Nickolas A, Wang Hongyang, Dimitrov Alexander, Davis Jon F, Jiang Zhuhua, Davis Christopher J, Gerstner Jason R
Washington State University Spokane.
Shanghai Academy of Agricultural Sciences.
Res Sq. 2024 Jan 18:rs.3.rs-3867797. doi: 10.21203/rs.3.rs-3867797/v1.
Sleep and circadian rhythm disruptions are comorbid features of many pathologies and can negatively influence numerous health conditions, including degenerative diseases, metabolic illnesses, cancer, and various neurological disorders. Genetic association studies linking sleep and circadian disturbances with disease susceptibility have mainly focused on changes in gene expression due to mutations, such as single-nucleotide polymorphisms. Thus, associations between sleep and/or circadian rhythm and alternative polyadenylation (APA), particularly in the context of other health challenges, are largely undescribed. APA is a process that generates various transcript isoforms from the same gene, resulting in effects on mRNA translation, stability, localization, and subsequent function. Here, we have identified unique APAs in rat brain that exhibit time-of-day-dependent oscillations in expression as well as APAs that are altered by sleep deprivation and the subsequent recovery period. Genes affected by APA usage include and . has two APAs which cycle with a 24 h period, one additional APA cycles with a 12 h period and one more that is reduced during recovery sleep. Finally, we compared sleep- or circadian-associated APAs with recently described APA-linked brain disorder susceptibility genes and found 46 genes in common.
睡眠和昼夜节律紊乱是许多疾病的共同特征，并且会对多种健康状况产生负面影响，包括退行性疾病、代谢性疾病、癌症以及各种神经障碍。将睡眠和昼夜节律紊乱与疾病易感性联系起来的遗传关联研究主要集中在由于突变（如单核苷酸多态性）导致的基因表达变化上。因此，睡眠和/或昼夜节律与可变聚腺苷酸化（APA）之间的关联，特别是在其他健康挑战的背景下，在很大程度上尚未得到描述。APA是一个从同一基因产生各种转录本异构体的过程，会影响mRNA的翻译、稳定性、定位及后续功能。在这里，我们在大鼠大脑中鉴定出了独特的APA，其表达呈现出昼夜依赖性振荡，以及受睡眠剥夺和随后恢复期影响而改变的APA。受APA使用影响的基因包括 和 。 有两个以24小时周期循环的APA，另外一个APA以12小时周期循环，还有一个在恢复睡眠期间减少。最后，我们将与睡眠或昼夜节律相关的APA与最近描述的与APA相关的脑疾病易感性基因进行了比较，发现有46个基因是共有的。
