On the functional relevance of spatiotemporally-specific patterns of experience-dependent long noncoding RNA expression in the brain.

The majority of transcriptionally active RNA derived from the mammalian genome does not code for protein. Long noncoding RNA (lncRNA) is the most abundant form of noncoding RNA found in the brain and is involved in many aspects of cellular metabolism. Beyond their fundamental role in the nucleus as decoys for RNA-binding proteins associated with alternative splicing or as guides for the epigenetic regulation of protein-coding gene expression, recent findings indicate that activity-induced lncRNAs also regulate neural plasticity. In this review, we discuss how lncRNAs may exert molecular control over brain function beyond their known roles in the nucleus. We propose that subcellular localization is a critical feature of experience-dependent lncRNA activity in the brain, and that lncRNA-mediated control over RNA metabolism at the synapse serves to regulate local mRNA stability and translation, thereby influencing neuronal function, learning and memory.