Multi-organelle-mediated mRNA localization in neurons and links to disease

Abstract

Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation of the proteome in distal outposts of neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial for neuron function and maintenance, and dysregulation of these processes can contribute to neurological disease. Recently, organelles have emerged as key players in regulating mRNA localization and local translation in dendrites and axons. In this review, we discuss the current evidence and open questions for this organelle-mediated mRNA localization. We highlight an emerging model in which multiple organelles create and orchestrate a subcellular microenvironment that can support precise mRNA localization and selective translation. This seems essential for maintaining organellar and neuronal function and health, as mutations in many of the involved proteins lead to various neurological disorders.