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RNA transport and local translation in neurodevelopmental and neurodegenerative disease

Nature Neuroscience volume 24, pages 622–632 (2021)Cite this article

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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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Fig. 1: The RNA transport apparatus in health and disease.
Fig. 2: Neuronal cis-acting RNA regulatory element structure, function, and dysfunction.
Fig. 3: Neuronal transport granule properties.
Fig. 4: Motor adaptors for RNA transport.
Fig. 5: The RNA transport apparatus and local metabolism.

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Acknowledgements

We thank B. Wu, A. Saric, J. Nixon-Abell, S. Qamar, S. Humble and J. Bonifacino for their careful reading and helpful comments on the manuscript, and we thank all of the laboratories and scientists who contributed to the data and discoveries described here. This work was supported by National Institute on Aging grant F30AG060722 (to M.S.F.), the NIH-Oxford-Cambridge Scholars Program (to M.S.F.), the El-Hibri Foundation (to M.S.F.), the Howard Hughes Medical Institute (to J.L.-S.) and the NIH Intramural Research Program (to M.E.W.)

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Authors and Affiliations

  1. Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Michael S. Fernandopulle & Michael E. Ward

  2. Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

    Michael S. Fernandopulle

  3. Medical Scientist Training Program, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Michael S. Fernandopulle

  4. Howard Hughes Medical Institute Janelia Research Campus, Ashburn, VA, USA

    Jennifer Lippincott-Schwartz

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  1. Michael S. Fernandopulle
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Fernandopulle, M.S., Lippincott-Schwartz, J. & Ward, M.E. RNA transport and local translation in neurodevelopmental and neurodegenerative disease. Nat Neurosci 24, 622–632 (2021). https://doi.org/10.1038/s41593-020-00785-2

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