A putative role for lncRNAs in epigenetic regulation of memory

The central dogma of molecular genetics is defined as encoded genetic information within DNA, transcribed into messenger RNA, which contain the instructions for protein synthesis, thus imparting cellular functionality and ultimately life. This molecular genetic theory has given birth to the field of neuroepigenetics, and it is now well established that epigenetic regulation of gene transcription is critical to the learning and memory process. In this review, we address a potential role for a relatively new player in the field of epigenetic crosstalk – long non-coding RNAs (lncRNAs). First, we briefly summarize epigenetic mechanisms in memory formation and examine what little is known about the emerging role of lncRNAs during this process. We then focus discussions on how lncRNAs interact with epigenetic mechanisms to control transcriptional programs under various conditions in the brain, and how this may be applied to regulation of gene expression necessary for memory formation. Next, we explore how epigenetic crosstalk in turn serves to regulate expression of various individual lncRNAs themselves. To highlight the importance of further exploring the role of lncRNA in epigenetic regulation of gene expression, we consider the significant relationship between lncRNA dysregulation and declining memory reserve with aging, Alzheimer's disease, and epilepsy, as well as the promise of novel therapeutic interventions. Finally, we conclude with a discussion of the critical questions that remain to be answered regarding a role for lncRNA in memory. • Epigenetic mechanisms drive transcriptional programs necessary for memory formation. • LncRNAs interact with key epigenetic mechanisms to regulate gene expression. • Aberrant expression of lncRNAs is associated with cellular dysfunction in cognitive disorders. • Expression of LncRNAs in the brain is region-specific, sex-specific and cell-type specific.