Abstract
Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.
Highlights
The formation of long-term memory, but not short-term memory, requires protein translation in neurons (Bramham and Wells, 2007; Costa-Mattioli et al, 2009)
Because frame shift occurs in the exon 5–6-deleted mRNA, most of the functional domains of RNG105 ranging from the N-terminal coiled-coil domain to the C-terminal RG-rich domain (a.a. 123–707) are deleted (Shiina et al, 2005)
Most of the exon 5–6-deleted mRNA appeared to be degraded by nonsense-mediated mRNA decay (NMD): in the hippocampus where Cre was highly expressed, expression of Rng105 transcripts from all exons was reduced to the comparable level to that of exon 5–6 transcripts as judged by RNA-seq analysis (Figure 1—figure supplement 1A)
Summary
The formation of long-term memory, but not short-term memory, requires protein translation in neurons (Bramham and Wells, 2007; Costa-Mattioli et al, 2009). Translation in neurons is regulated globally and locally in dendrites near stimulated postsynaptic sites (Aakalu et al, 2001; Yoon et al, 2016). This local translation is involved in the regulation of synaptic plasticity and functions, and mediated by dendritic mRNA transport by ‘RNA granules’, membrane-less macromolecular assemblies of mRNAs, ribosomes, and RNA-binding proteins
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