Nucleolin-Mediated RNA Localization Regulates Neuron Growth and Cycling Cell Size

• A kinesin-nucleolin complex transports size-regulating mRNAs to the cell periphery
• Importin β1 mRNA MAIL motif associates with nucleolin to regulate growth and size
• Sequestration of nucleolin or importin β1 enhances growth and shifts protein synthesis
• Subcellular mRNA localization regulates size and growth in neurons and cycling cells

SummaryHow can cells sense their own size to coordinate biosynthesis and metabolism with their growth needs? We recently proposed a motor-dependent bidirectional transport mechanism for axon length and cell size sensing, but the nature of the motor-transported size signals remained elusive. Here, we show that motor-dependent mRNA localization regulates neuronal growth and cycling cell size. We found that the RNA-binding protein nucleolin is associated with importin β1 mRNA in axons. Perturbation of nucleolin association with kinesins reduces its levels in axons, with a concomitant reduction in axonal importin β1 mRNA and protein levels. Strikingly, subcellular sequestration of nucleolin or importin β1 enhances axonal growth and causes a subcellular shift in protein synthesis. Similar findings were obtained in fibroblasts. Thus, subcellular mRNA localization regulates size and growth in both neurons and cycling cells.

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