On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons.
Autor: | Shigeoka T; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: ts561@cam.ac.uk., Koppers M; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Wong HH; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Lin JQ; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Cagnetta R; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Dwivedy A; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., de Freitas Nascimento J; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., van Tartwijk FW; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK., Ströhl F; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK., Cioni JM; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Schaeffer J; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Carrington M; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., Kaminski CF; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK., Jung H; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Harris WA; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK., Holt CE; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: ceh33@cam.ac.uk. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2019 Dec 10; Vol. 29 (11), pp. 3605-3619.e10. |
DOI: | 10.1016/j.celrep.2019.11.025 |
Abstrakt: | Ribosome assembly occurs mainly in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) in axons, far away from neuronal cell bodies. Here, we report a physical and functional interaction between locally synthesized RPs and ribosomes in the axon. We show that axonal RP translation is regulated through a sequence motif, CUIC, that forms an RNA-loop structure in the region immediately upstream of the initiation codon. Using imaging and subcellular proteomics techniques, we show that RPs synthesized in axons join axonal ribosomes in a nucleolus-independent fashion. Inhibition of axonal CUIC-regulated RP translation decreases local translation activity and reduces axon branching in the developing brain, revealing the physiological relevance of axonal RP synthesis in vivo. These results suggest that axonal translation supplies cytoplasmic RPs to maintain/modify local ribosomal function far from the nucleolus in neurons. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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