Regulation of Neuronal RNA Granule Dynamics Through Phase Separation in Memory Formation and Disease

Local translation in neuronal dendrites is an important basis for synaptic plasticity that underlies long-term memory formation. RNA granules, which are dynamic condensates consisting of mRNAs, ribosomes, and RNA-binding proteins, are essential for transporting mRNAs to dendrites and regulating local dendritic translation. Through coordinating and modulating the translation of specific mRNAs, these granules enable neurons to refine synaptic connections in response to synaptic inputs at the appropriate temporal and spatial scales. Recent studies have revealed that RNA granules form through liquid–liquid phase separation (LLPS), which allows them to adapt to changes in synaptic inputs and switch between different translational states. However, dysregulation of RNA granule dynamics, particularly the formation of aberrant aggregates, has been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Thus, RNA granules play a pivotal role in maintaining synaptic plasticity and cognitive function in healthy neurons, while their dysregulation may contribute to neurodegeneration.