TY - JOUR
T1 - On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons
AU - Shigeoka, Toshiaki
AU - Koppers, Max
AU - Wong, Hovy Ho-Wai
AU - Lin, Julie Qiaojin
AU - Cagnetta, Roberta
AU - Dwivedy, Asha
AU - de Freitas Nascimento, Janaina
AU - van Tartwijk, Francesca W.
AU - Ströhl, Florian
AU - Cioni, Jean-Michel
AU - Schaeffer, Julia
AU - Carrington, Mark
AU - Kaminski, Clemens F.
AU - Jung, Hosung
AU - Harris, William A.
AU - Holt, Christine E.
PY - 2019/12/10
Y1 - 2019/12/10
N2 - © 2019 The AuthorsRibosome 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. © 2019 The AuthorsLocal protein synthesis in axons supplies new ribosomal proteins far from the nucleolus, the known site of ribosome biogenesis. Shigeoka et al. provide evidence that axonally synthesized ribosomal proteins join pre-existing ribosomes and maintain translation activity in axons, which is required for axon terminal branching.
AB - © 2019 The AuthorsRibosome 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. © 2019 The AuthorsLocal protein synthesis in axons supplies new ribosomal proteins far from the nucleolus, the known site of ribosome biogenesis. Shigeoka et al. provide evidence that axonally synthesized ribosomal proteins join pre-existing ribosomes and maintain translation activity in axons, which is required for axon terminal branching.
UR - https://www.scopus.com/pages/publications/85076052709
UR - https://www.scopus.com/pages/publications/85076052709#tab=citedBy
U2 - 10.1016/j.celrep.2019.11.025
DO - 10.1016/j.celrep.2019.11.025
M3 - Article
SN - 2211-1247
VL - 29
SP - 3605-3619.e10
JO - Cell Reports
JF - Cell Reports
IS - 11
ER -