University of Minnesota, St. Paul, MN, 55108, United States.
University of Minnesota, St. Paul, MN, 55108, United States.
Neurosci Biobehav Rev. 2021 Dec;131:988-1004. doi: 10.1016/j.neubiorev.2021.09.049. Epub 2021 Sep 28.
The circadian rhythm of the human brain is attuned to sleep-wake cycles that entail global alterations in neuronal excitability. This periodicity involves a highly coordinated regulation of gene expression. A growing number of studies are documenting a fascinating connection between primate-specific retrotransposons (Alu elements) and key epigenetic regulatory processes in the primate brain. Collectively, these studies indicate that Alu elements embedded in the human neuronal genome mediate post-transcriptional processes that unite human-specific neuroepigenetic landscapes and circadian rhythm. Here, we review evidence linking Alu retrotransposon-mediated posttranscriptional pathways to circadian gene expression. We hypothesize that Alu retrotransposons participate in the organization of circadian brain function through multidimensional neuroepigenetic pathways. We anticipate that these pathways are closely tied to the evolution of human cognition and their perturbation contributes to the manifestation of human-specific neurological diseases. Finally, we address current challenges and accompanying opportunities in studying primate- and human-specific transposable elements.
人类大脑的昼夜节律与睡眠-觉醒周期相协调，这需要神经元兴奋性的全局改变。这种周期性涉及基因表达的高度协调调控。越来越多的研究记录了灵长类动物特异性逆转录转座子（Alu 元件）与灵长类动物大脑中关键表观遗传调控过程之间引人入胜的联系。总的来说，这些研究表明，嵌入人类神经元基因组中的 Alu 元件介导了将人类特异性神经表观遗传景观和昼夜节律联系起来的转录后过程。在这里，我们回顾了将 Alu 逆转录转座子介导的转录后途径与昼夜节律基因表达联系起来的证据。我们假设 Alu 逆转录转座子通过多维神经表观遗传途径参与昼夜节律大脑功能的组织。我们预计这些途径与人类认知的进化密切相关，其干扰导致了人类特异性神经疾病的表现。最后，我们讨论了在研究灵长类动物和人类特异性转座元件时当前面临的挑战和伴随的机遇。
