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2016

Cell Rep. 2016 Aug 9;16(6):1664-76. doi: 10.1016/j.celrep.2016.07.005. Epub 2016 Jul 28.

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

RB Perry;I Rishal;E Doron-Mandel;AL Kalinski;KF Medzihradszky;M Terenzio;S Alber;S Koley;A Lin;M Rozenbaum;D Yudin;PK Sahoo;C Gomes;V Shinder;W Geraisy;EA Huebner;CJ Woolf;A Yaron;AL Burlingame;JL Twiss;M Fainzilber

Weizmann Institute of Science, Rehovot 76100, Israel. University of South Carolina, Columbia, SC 29208; University of California, San Francisco, CA 94158; Boston Children's Hospital and Harvard Medical School, MA 02115, USA.

Service type: Knockout mice

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.

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