RNG105/caprin1, an RNA granule protein for dendritic mRNA localization, is essential for long-term memory formation

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.

Liquid- and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules

“…RNA granule scaffolds play key roles, especially in the brain. Their functions are involved in learning and memory (34), and abnormalities in their dynamics are associated with neurodegenerative diseases (8,9). Therefore, it is important to understand the relationship between the dynamics of RNA granules and neural functions.…”

Joining the dots – protein‐RNA interactions mediating local mRNA translation in neurons

“…Interestingly, the direct visualisation of a smaller number (71) of chosen mRNAs, using high-resolution FISH indicated that different mRNAs have a different distribution along the dendrites, which underlies the complexity of mRNA localisation [6]. The large size and diversity of the pool of neurite-enriched mRNAs has been confirmed by several recent studies performed both in hippocampal brain sections [13,14] and in cells [15][16][17]. The analysis indicates that 1000-3000 mRNAs are differentially distributed between the neuronal soma and neurites.…”

RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether

“…In neurons, LAMP1-positive vesicles include both degradative lysosomes and non-acidic endolysosomes (Cheng et al, 2018;Farías et al, 2017), but for simplicity, we hereafter refer to all LAMP1 positive structures as lysosomes. Within axons, lysosomes co-trafficked with RNA granules labeled with G3BP1 (Sahoo et al 2018), TDP-43 (Alami et al, 2014;Gopal et al, 2017), and CAPRIN1 (Nakayama et al, 2017) ( Figure 1D, Supplemental Figure 1J, K). Lysosomes also co-trafficked with actin-MS2/MCP ( Figure 1E, supplemental Figure 1I), a probe that labels actin mRNA, one of the most abundant mRNAs in axons (Bassell et al, 1998).…”