scholarly journals Monosomes actively translate synaptic mRNAs in neuronal processes

2019 ◽  
Author(s):  
Anne Biever ◽  
Caspar Glock ◽  
Georgi Tushev ◽  
Elena Ciirdaeva ◽  
Julian D. Langer ◽  
...  

AbstractIn order to deal with their huge volume and complex morphology, neurons localize mRNAs and ribosomes near synapses to produce proteins locally. A relative paucity of polyribosomes (considered the active sites of translation) detected in electron micrographs of neuronal processes (axons and dendrites), however, has suggested a rather limited capacity for local protein synthesis. Polysome profiling together with ribosome footprinting of microdissected synaptic regions revealed that a surprisingly high number of dendritic and/or axonal transcripts were predominantly associated with monosomes (single ribosomes). Contrary to prevailing views, the neuronal monosomes were in the process of active protein synthesis (e.g. they exhibited elongation). Most mRNAs showed a similar translational status in both compartments, but some transcripts exhibited differential ribosome occupancy in the somata and neuropil. Strikingly, monosome-preferred transcripts often encoded high-abundance synaptic proteins. This work suggests a significant contribution of monosome translation to the maintenance of the local neuronal proteome. This mode of translation can presumably solve some of restricted space issues (given the large size of polysomes) and also increase the diversity of proteins made from a limited number of ribosomes available in dendrites and axons.

Science ◽  
2020 ◽  
Vol 367 (6477) ◽  
pp. eaay4991 ◽  
Author(s):  
Anne Biever ◽  
Caspar Glock ◽  
Georgi Tushev ◽  
Elena Ciirdaeva ◽  
Tamas Dalmay ◽  
...  

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.


2021 ◽  
Author(s):  
Clémence Bernard ◽  
David Exposito-Alonso ◽  
Martijn Selten ◽  
Stella Sanalidou ◽  
Alicia Hanusz-Godoy ◽  
...  

Neurons use local protein synthesis as a mechanism to support their morphological complexity, which requires independent control across multiple subcellular compartments including individual synapses. However, to what extent local translation is differentially regulated at the level of specific synaptic connections remains largely unknown. Here, we identify a signaling pathway that regulates the local synthesis of proteins required for the formation of excitatory synapses on parvalbumin-expressing (PV+) interneurons in the mouse cerebral cortex. This process involves the regulation of the mTORC1 inhibitor Tsc2 by the receptor tyrosine kinase ErbB4, which enables the local control of mRNA translation in a cell type-specific and synapse-specific manner. Ribosome-associated mRNA profiling reveals a molecular program of synaptic proteins that regulates the formation of excitatory inputs on PV+ interneurons downstream of ErbB4 signaling. Our work demonstrates that local protein translation is regulated at the level of specific connections to control synapse formation in the nervous system.


Neuroreport ◽  
2003 ◽  
Vol 14 (10) ◽  
pp. 1357-1360 ◽  
Author(s):  
J. Brian McCarthy ◽  
Teresa A. Milner

2013 ◽  
Vol 106 ◽  
pp. 246-257 ◽  
Author(s):  
Daniele Lana ◽  
Francesca Cerbai ◽  
Jacopo Di Russo ◽  
Francesca Boscaro ◽  
Ambra Giannetti ◽  
...  

2015 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Michael Piper ◽  
Aih Lee ◽  
Francisca van Horck ◽  
Heather McNeilly ◽  
Trina Lu ◽  
...  

2019 ◽  
Vol 139 ◽  
pp. 26-36 ◽  
Author(s):  
Sandip Koley ◽  
Meir Rozenbaum ◽  
Mike Fainzilber ◽  
Marco Terenzio

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Claudia M. Fusco ◽  
Kristina Desch ◽  
Aline R. Dörrbaum ◽  
Mantian Wang ◽  
Anja Staab ◽  
...  

AbstractOwing 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.


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