The m6A-epitranscriptome in brain plasticity, learning and memory

Abstract

Activity-dependent gene expression and protein translation underlie the ability of neurons to dynamically adjust their synaptic strength in response to sensory experience and during learning. The emerging field of epitranscriptomics (RNA modifications) has rapidly shifted our views on the mechanisms that regulate gene expression. Among hundreds of biochemical modifications on RNA, N⁶-methyladenosine (m⁶A) is the most abundant reversible mRNA modification in the brain. Its dynamic nature and ability to regulate all aspects of mRNA processing have positioned m⁶A as an important and versatile regulator of nervous system functions, including neuronal plasticity, learning and memory. In this review, we summarise recent experimental evidence that supports the role of m⁶A signalling in learning and memory, as well as providing an overview of the underlying molecular mechanisms in neurons. We also discuss the consequences of perturbed m⁶A signalling and/or its regulatory networks which are increasingly being linked to various cognitive disorders in humans.

Keywords: Cognitive dysfunctions; N(6)-methyladenosine; Neurological disorders; Neuronal plasticity; RNA metabolism; RNA modifications.