Rose Marie Akiki, Sierra Simmerson, Caila Worley, Rebecca G Cornbrooks, Kosuke Magami, Alain Greige, Kristen K Snyder, Daniel J. Wood, Mary Claire Herrington, Philip Mace, Kyle Blidy, Nobuya Koike, Stefao Berto, Christopher W. Cowan, Makoto Taniguchi

Emotional experiences often drive behavioral responses that enable organisms adapt to their environment. These experiences trigger the expression of specific gene, initiating transcriptional programs that underlie cellular, synaptic, and behavioral plasticity. This gene expression is tightly regulated and plays critical role in adaptive responses to emotional stimuli. Conversely, dysregulation of these transcriptional program is implicated in maladaptive behaviors associated with neuropsychiatric disorders, including mood and substance use disorder (SUD). We recently demonstrated that long non-coding RNAs (lncRNAs) form DNA:RNA hybrid structure, R-loops, across the genome. Genes associated with these R-loops are identified in the glutamatergic and dopaminergic signaling pathways, calcium signaling pathways, and synaptic plasticity-related genes. We discovered that neuronal activity induces the formation of R-loop at the enhancer region of immediate early gene, Npas4, a gene that we previously identified as a key regulator of stress-induced anhedonia-like behavior and drug reward-associated contextual memory. This R-loop is essential for linking distal enhancer to the proximal promoter, facilitating Npas4 gene expression, and regulating cocaine reward-associated contextual memory. Together, these data identify R-loops as novel regulatory mechanism that translates emotional experience into gene expression and behavioral plasticity. In this presentation, we will discuss the functional mechanisms of R-loops in gene expression and behavior in response to emotional experiences.

Department of Neuroscience, Medical University of South Carolina

Funding support: NIH_T32 DA07288, R01 DA032708, R01 MH129521, P20 GM140964, P20 GM148302, P50 DA046373, and UL1 TR001450.