Portal de Periódicos da CAPES

Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression

2020; Cell Press; Volume: 106; Issue: 6 Linguagem: Inglês

10.1016/j.neuron.2020.03.023

1097-4199

Orna Issler, Yentl Y. van der Zee, Aarthi Ramakrishnan, Junshi Wang, Chunfeng Tan, Yong‐Hwee Eddie Loh, Immanuel Purushothaman, Deena M. Walker, Zachary S. Lorsch, Peter J. Hamilton, Catherine J. Peña, Erin Flaherty, Brigham J. Hartley, Angélica Torres‐Berrío, Eric M. Parise, Hope Kronman, Julia E. Duffy, Molly Estill, Erin S. Calipari, Benoît Labonté, Rachael L. Neve, Carol A. Tamminga, Kristen Brennand, Yan Dong, Li Shen, Eric J. Nestler,

Circular RNAs in diseases

Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males. Using viral-mediated gene transfer to express LINC00473 in adult mouse PFC neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates LINC00473 as a CREB effector. Together, our studies identify LINC00473 as a female-specific driver of stress resilience that is aberrant in female depression.