Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins

Claudia M Fusco,Veronica Villeri,Anja Staab,Eleanor Vail,Julian D Langer,Erin M Schuman,Ivy C W Chan,Aline R Dörrbaum,Mantian Wang,Kristina Desch

doi:10.1038/s41467-021-26365-x

Abstract

Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.

Highlights

Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using messenger RNAs (mRNAs) and ribosomes present in the neuropil
Advances in transcriptome-wide profiling methods have led to the elucidation of thousands of mRNAs localized to neuronal processes
To evaluate whether the mRNAs for the ribosome are enriched in dendrites and axons, we compared the dendritic enrichment of ribosomal protein (RP) mRNAs to mRNAs that code for proteins in other ubiquitous macromolecular complexes

Summary

Introduction

Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). The above data suggest that the protein composition of ribosomes might not be fixed after biogenesis, but rather remain susceptible to dynamic association or exchange of RPs with mature ribosomes. To address this possibility in rodent neurons, we first used high-resolution fluorescence in situ hybridization (FISH) to directly detect a large population of RP mRNAs in neuronal cell bodies and dendrites. We found that the incorporation probability of some RPs was regulated by the subcellular compartment (neurites vs cell bodies) and by changes in the physiological state (following oxidative stress) Taken together, these data suggest that neurons can dynamically regulate RPs incorporation into ribosomes in space and time

Methods

Results

Conclusion