On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons

Abstract

Summary: 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. : Local 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. Keywords: axon, mRNA, local translation, ribosome, ribosomal proteins, Rps4x, axonal protein synthesis, ribosome remodeling, axon branching, neural wiring