A cAMP/PKA-dependent synaptically targeted lncRNA mediates structural plasticity in hippocampal neurons by functionally interacting with the Spectrin/Ankyrin Network

Abstract

Activity dependent structural plasticity at the synapse requires specific changes in the neuronal transcriptome. While much is known about the role of coding elements in this process, the role of the long-noncoding transcriptome remains elusive. Here we report the discovery of an intronic long noncoding RNA (lncRNA),termed ADEPTR, whose expression is upregulated and is synaptically transported in a cAMP/PKA dependent manner in hippocampal neurons, independent of its protein-coding host gene. Loss of ADEPTR function suppresses activity-dependent changes in synaptic transmission and structural plasticity of dendritic spines. Mechanistically, dendritic localization of ADEPTR is mediated by molecular motor protein Kif2A. ADEPTR physically binds to actin-scaffolding regulators Ankyrin (AnkB) and Spectrin (Sptn1) and is required for their dendritic localization. Taken together, this study demonstrates that ADEPTR regulates the dendritic Spectrin-Ankyrin network for structural plasticity at the synapse and illuminates a novel role for lncRNAs at the synapse.

Non-coding RNAs in the brain: new class of prospective biomarkers and therapeutics

“…The experimental knockdown of this lncRNA in mice led to a reduced neuronal plasticity in response to activity. 84 A specific lncRNA, GM12371, regulates several genes linked to the shape and signaling capacity of the developing neurons as part of the CNS development and functioning. The learning related signal in mouse hippocampal cells up-regulates the expression of GM12371 whereas its reduction results in inactive neurons.…”