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Cited by 183RNA Research and SplicingGenetics and Neurodevelopmental DisordersRNA and protein synthesis mechanisms

RNA transport and local translation in neurodevelopmental and neurodegenerative disease

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Fernandopulle, Michael S., Lippincott-Schwartz, Jennifer, Ward, Michael E.·2021·Nature Neuroscience
DOI 10.1038/s41593-020-00785-2PMC PMC8860725
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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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  • Expressed MAP2 without any native mRNA structures such as a 3′-untranslated region still localizes properly to dendrites.

    “However, we (this paper) and others have shown that expressed MAP2 without any native mRNA structures such as a 3′-untranslated region, which are typically necessary for mRNA transport and local translation (55), still localizes properly to dendrites (11).”

    From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [55]

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Authors
Fernandopulle, M. S., Lippincott-Schwartz, J., & Ward, M. E.
Affiliations
  • Northwestern University (US)
  • National Institutes of Health (US)
Corresponding author
Ward, Michael E.
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2021-01-28
Volume
24
Issue
5
Pages
622-632
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-020-00785-2
PMC
PMC8860725
OpenAlex
W3122919571
Cited by
183
References
8
Citations by year
2026: 34 · 2025: 37 · 2024: 35 · 2023: 32 · 2022: 27 · 2021: 18
FWCI
3.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (Z99 NS999999)
  • National Institute on Aging (F30AG060722)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
RNA transport, local translation, neurodegenerative diseases, neurodevelopmental disorders, RNA regulatory elements, dendritic protein synthesis, axonal transport
MeSH terms
Animals, Biological Transport, Brain, Humans, Neurons, Protein Biosynthesis, Neurodegenerative Diseases, RNA Transport, Neurodevelopmental Disorders

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