RNA transport and local translation in neurodevelopmental and neurodegenerative disease

Neurons decentralize protein synthesis from the cell body to support the active metabolism of remote dendritic and axonal compartments. The neuronal RNA transport apparatus, composed of cis-acting RNA regulatory elements, neuronal transport granule proteins, and motor adaptor complexes, drives the long-distance RNA trafficking required for local protein synthesis. Over the past decade, advances in human genetics, subcellular biochemistry, and high-resolution imaging have implicated each member of the apparatus in several neurodegenerative diseases, establishing failed RNA transport and associated processes as a unifying pathomechanism. In this review, we deconstruct the RNA transport apparatus, exploring each constituent's role in RNA localization and illuminating their unique contributions to neurodegeneration. RNA localization is a defining and intricately regulated feature of neuronal physiology. Fernandopulle et al. review how altered RNA transport and local translation might inform understanding of neuronal disease.

Automated summary

The RNA transport apparatus in neurons plays a crucial role in local protein synthesis, and its dysfunction is implicated in various neurodegenerative diseases. This mechanism serves as a unifying pathomechanism for neurodegenerative diseases, highlighting the importance of understanding altered RNA transport and local translation in neuronal diseases.