Silc1 long noncoding RNA is required for efficient memory formation

ABSTRACT: A rich repertoire of long noncoding RNAs (lncRNAs) is expressed in the mammalian nervous system, but their significance and functions remain largely unknown. Co-expression analysis, referred to as guilt-by-association, is often used as a proxy for prediction of lncRNA function, but the validity of the assumptions of this approach remains unclear. Here, we study the functions in the central nervous system of Silc1, a lncRNA we previously shown to be important for neuroregeneration in the peripheral nervous system. Silc1 is located in a gene desert ~200 Kb away from its cis-regulated target gene, Sox11. Silc1 is broadly expressed in the adult brain, and surprisingly, in the hippocampus Silc1 and Sox11 are anti-correlated in their expression domains. Despite this, upon exposure to novel environment, Silc1 transcription or its RNA product are important for proper induction of Sox11 mRNA and protein throughout CA1-3, and for proper expression of key Sox11 target genes. Furthermore, an intact Silc1 is required for efficient spatial learning (but notably not for memory retrieval). Silc1 levels decline during aging and in models of Alzheimer’s disease. Overall, we uncover a novel pathway, acting in mature neurons, which need Silc1 to activate Sox11, a transcription factor mostly studied exclusively in the context of immature neurons, and in turn to induce a neuronal growth-associted transcriptional program required for efficient memory formation.

ORGANISM(S): Mus musculus

PROVIDER: GSE216643 | GEO | 2023/07/29

REPOSITORIES: GEO