RNA transport and local translation in neurodevelopmental and neurodegenerative disease

Nat Neurosci. 2021 May;24(5):622-632. doi: 10.1038/s41593-020-00785-2. Epub 2021 Jan 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Brain / metabolism*
  • Humans
  • Neurodegenerative Diseases / metabolism*
  • Neurodevelopmental Disorders / metabolism*
  • Neurons / metabolism*
  • Protein Biosynthesis / physiology*
  • RNA Transport / physiology*