RNA transport and local translation in neurodevelopmental and neurodegenerative disease

MS Fernandopulle, J Lippincott-Schwartz… - Nature …, 2021 - nature.com
MS Fernandopulle, J Lippincott-Schwartz, ME Ward
Nature neuroscience, 2021nature.com
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 …
Abstract
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.
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