Primate-specific retrotransposons and the evolution of circadian networks in the human brain

•A number of studies have linked Alu retrotransposon-mediated molecular processes to circadian gene expression pathways.•We review the evidence indicating Alu RNAs are essential for posttranscriptional regulation of circadian gene expression.•Alus likely participate in the organization of circadian brain function, operating in multidimensional neuroepigenetic space.•Perturbations of Alu-centric posttranscriptional pathways likely contribute to the manifestation of neurological disease. 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.