The Role of RNA-protein Granules in Neurodevelopment

RNA-protein granules are dynamic, membrane-less organelles found in the nucleus and cytoplasm of cells across nearly all organisms, from the unicellular to the multicellular. They are complex assemblies composed of coding and non-coding RNAs, RNA-binding proteins, enzymes, and other proteins. Functionally, they are hubs for RNA storage, transport and regulation of translation. A growing body of evidence now underscores their critical role in orchestrating processes within brain development. These granules facilitate neurodevelopment through the spatiotemporal regulation of gene expression, ensuring proteins are synthesized in the right place and time. For instance, the initial division and differentiation of neural precursor cells rely on mechanisms like transcriptional priming, a process facilitated by specific granules—processing bodies. As brain cells mature, RNA-protein granules enable the transport of transcripts to distant cellular sites. There, they regulate local protein synthesis, which is fundamental for cellular morphology, the maturation of dendritic spines, synaptic plasticity, and overall neural circuit connectivity. Furthermore, stress granules, which form transiently in response to cellular stress, are increasingly recognized as players in the developing central nervous system. It is hypothesized that stress granules promote cell survival during stressful events often accompanying embryonic development. Importantly, mutations in genes encoding RNA-protein granule proteins are associated with an increased risk for neurodevelopmental disorders. These mutations disrupt the dynamic nature of RNA-protein granules, leading to disturbances in mRNA localization and expression. Neurodevelopmental disorders linked to these mutations are often characterized by intellectual disability, speech delay, epileptic seizures, and autism spectrum disorder. This review will summarize the current data on the role of these RNA-protein granules–with a focus on stress granules, processing bodies, and transport granules–in shaping brain development.