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

• Published in: Nature communications Vol. 12; no. 1; p. 6127
• Main Authors: Fusco, Claudia M., Desch, Kristina, Dörrbaum, Aline R., Wang, Mantian, Staab, Anja, Chan, Ivy C. W., Vail, Eleanor, Villeri, Veronica, Langer, Julian D., Schuman, Erin M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.10.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/32; 38; 38/91; 631/378/340; 631/80/85; Animals; Axons; Axons - metabolism; Biosynthesis; Cells, Cultured; Cytoplasm; Dendrites; Female; Humanities and Social Sciences; Male; Mass spectrometry; Mass spectroscopy; multidisciplinary; Neurites - metabolism; Neurons - metabolism; Neuropil; Neuropil - metabolism; Nuclei (cytology); Oxidative stress; Protein Biosynthesis; Protein synthesis; Proteins; Proteomes; Rats; Rats, Sprague-Dawley; Ribosomal proteins; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; Ribosomes; Ribosomes - genetics; Ribosomes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Synapses; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26365-x

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. Ribosomes, assembled in the nucleus and perinuclear region, are thought to remain invariant throughout their lifetime. Here the authors document the dynamic association or exchange of ribosomal proteins within mature ribosomes of neuronal cells.