Distinct Dynamics and Composition of Endogenous Neuronal RNA Granules

The localized transcriptome is diverse; however, how different mRNAs are organized into granules for efficient localization and translation remains unknown. Here, we combine real time single RNA imaging with protein and RNA proximity labeling to investigate two endogenous neuronal mRNA granule populations, Actb and Arc, in stimulated primary hippocampal neurons.

Using orthogonal RNA labeling systems in a dual knock-in mouse model, we show that Actb and Arc mRNAs are packaged into spatially segregated granules with distinct trafficking dynamics, localization kinetics, and responses to synaptic stimulation. While Actb granules displayed rapid and sustained localization, whereas Arc granules showed delayed, transient recruitment, consistent with their respective roles in structural and activity-dependent plasticity.