Year: 2019
Type: article
Abstract: 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.
Source: Cell Reports
Authors: Toshiaki Shigeoka, Max Koppers, Hovy Ho-Wai Wong, Julie Qiaojin Lin, Roberta Cagnetta, Asha Dwivedy, Janaina de Freitas Nascimento, Francesca W. van Tartwijk, Florian Ströhl, Jean-Michel Cioni, Julia Schaeffer, Mark Carrington, Clemens F. Kaminski, Hosung Jung, William A. Harris, Christine E. Holt
Institution: University of Cambridge
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1417656367, EPSRC Centre for Doctoral Training (CDT) in Sensor Technologies and Application, G2561383389, MICA: Multi-parametric and super-resolution imaging of amyloidogenic proteins, G404389588, Development of single molecule techniques for nanoscale imaging of toxic protein species in vitro and in cells., How to build a retina., Liquid droplets and hydrogels: protein phase transition in health and disease, The effect of FUS phase transitions on local protein synthesis in axon termini and the implications for neurodegeneration, Mechanisms of neurotoxicity of amyloid aggregates., G5358911175, Next generation live super-resolution microscopy: development and application at the Cambridge Advanced Imaging Centre, G5859390703, Axon survival: the role of protein synthesis, G7413148874, G7555549168, G7823050896, G8031980269, G8039008064, Axon navigation in the developing brain.
OpenAlex ID: W2995312562