Transcriptomic analysis identifies synapse-enriched lncRNAs required for excitatory synapse development and fear memory

Abstract

Characterization of brain-enriched lncRNAs have predominantly been restricted to the nuclear compartment; with limited exploration of synaptic lncRNA functions. Our RNA-seq analysis of synaptoneurosomes identify 94 synaptically-enriched lncRNAs in the adult mouse hippocampus. Among these, we characterized the roles of Pantr1, Pvt1 and 2410006H16Rik (named SynLAMP) in glutamatergic synapse development, plasticity and memory. Pvt1 regulates dendritic arborization, spine morphology and glutamatergic synapse formation via a molecular framework of synaptogenic genes; as detected by RNA-seq analysis of the hippocampal trancriptome following Pvt1 knockdown. SynLAMP and Pantr1 modulate mEPSC amplitude and surface AMPA receptor distribution in mature synapses. We find activity-invoked redistribution of these synaptic lncRNAs and their concommitant reversible association with RNA binding proteins. The activity-dependent, transcript-specific synaptic localization of SynLAMP and Pantr1 indicate their synapse-centric function. SynLAMP specifically regulates basal and activity-invoked nascent translation in somato-dendritic compartments and its RNAi disrupts memory consolidation, underlining its input-specific role in synaptic translation.