Spatiotemporal Insights Into RNA–Organelle Interactions in Neurons

Neurons exhibit spatial compartmentalization of gene expression where localization of messenger RNAs (mRNAs) to distal processes allows for site-specific distribution of proteins through local translation. Recently, there have been reports of coordination between mRNA transport with vesicular and organellar trafficking. In this review, we will highlight the latest literature on axonal and dendritic local protein synthesis with links to mRNA–organelle cotransport followed by emerging technologies necessary to study these phenomena. Recent high-resolution imaging studies have led to insights into the dynamics of RNA–organelle interactions, and we can now peer into these intricate interactions within subcellular compartments of neurons.

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Monosomes actively translate synaptic mRNAs in neuronal processes

Science ◽

10.1126/science.aay4991 ◽

2020 ◽

Vol 367 (6477) ◽

pp. eaay4991 ◽

Cited By ~ 26

Author(s):

Anne Biever ◽

Caspar Glock ◽

Georgi Tushev ◽

Elena Ciirdaeva ◽

Tamas Dalmay ◽

...

Keyword(s):

Protein Synthesis ◽

Active Sites ◽

Synaptic Proteins ◽

Messenger Rnas ◽

Local Protein Synthesis ◽

Relative Paucity ◽

Polysome Profiling ◽

Neuronal Processes ◽

Ribosome Footprinting ◽

Local Protein

To accommodate their complex morphology, neurons localize messenger RNAs (mRNAs) and ribosomes near synapses to produce proteins locally. However, a relative paucity of polysomes (considered the active sites of translation) detected in electron micrographs of neuronal processes has suggested a limited capacity for local protein synthesis. In this study, we used polysome profiling together with ribosome footprinting of microdissected rodent synaptic regions to reveal a surprisingly high number of dendritic and/or axonal transcripts preferentially associated with monosomes (single ribosomes). Furthermore, the neuronal monosomes were in the process of active protein synthesis. Most mRNAs showed a similar translational status in the cell bodies and neurites, but some transcripts exhibited differential ribosome occupancy in the compartments. Monosome-preferring transcripts often encoded high-abundance synaptic proteins. Thus, monosome translation contributes to the local neuronal proteome.

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Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments

Science ◽

10.1126/science.aau3644 ◽

2019 ◽

Vol 364 (6441) ◽

pp. eaau3644 ◽

Cited By ~ 88

Author(s):

Anne-Sophie Hafner ◽

Paul G. Donlin-Asp ◽

Beulah Leitch ◽

Etienne Herzog ◽

Erin M. Schuman

Keyword(s):

Protein Synthesis ◽

Mouse Brain ◽

Metabolic Labeling ◽

Messenger Rnas ◽

Presynaptic Terminals ◽

Ample Evidence ◽

Local Protein Synthesis ◽

Neuronal Dendrites ◽

Brain Synaptosomes ◽

Local Protein

There is ample evidence for localization of messenger RNAs (mRNAs) and protein synthesis in neuronal dendrites; however, demonstrations of these processes in presynaptic terminals are limited. We used expansion microscopy to resolve pre- and postsynaptic compartments in rodent neurons. Most presynaptic terminals in the hippocampus and forebrain contained mRNA and ribosomes. We sorted fluorescently labeled mouse brain synaptosomes and then sequenced hundreds of mRNA species present within excitatory boutons. After brief metabolic labeling, >30% of all presynaptic terminals exhibited a signal, providing evidence for ongoing protein synthesis. We tested different classic plasticity paradigms and observed distinct patterns of rapid pre- and/or postsynaptic translation. Thus, presynaptic terminals are translationally competent, and local protein synthesis is differentially recruited to drive compartment-specific phenotypes that underlie different forms of plasticity.

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