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

Elife. 2017 Nov 21;6:e29677. doi: 10.7554/eLife.29677.

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.

Keywords: RNA granule; RNG105/caprin1; cell biology; long-term memory; mRNA localization; mouse; neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Dendrites / metabolism*
  • Gene Deletion
  • Gene Expression
  • Gene Expression Profiling
  • Hippocampus / physiology*
  • Learning
  • Memory, Long-Term*
  • Mice
  • RNA, Messenger / metabolism*
  • Receptors, Glutamate / biosynthesis

Substances

  • Caprin1 protein, mouse
  • Cell Cycle Proteins
  • RNA, Messenger
  • Receptors, Glutamate

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.