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

Cell Rep. 2016 Aug 9;16(6):1664-1676. doi: 10.1016/j.celrep.2016.07.005. Epub 2016 Jul 28.

Abstract

How 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.

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Size*
  • Mice, Transgenic
  • Motor Neurons / metabolism*
  • Neurogenesis
  • Nucleolin
  • Phosphoproteins / metabolism*
  • Protein Biosynthesis / physiology
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*

Substances

  • Phosphoproteins
  • RNA, Messenger
  • RNA-Binding Proteins