title: Nucleolin-Mediated RNA Localization Regulates Neuron Growth and Cycling Cell Size.
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.
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Rotem Ben-Tov
authors.initials: RB
authors.lastname: Perry
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ida
authors.initials: I
authors.lastname: Rishal
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Doron-Mandel
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Kalinski
authors.affiliation: Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Katalin F
authors.initials: KF
authors.lastname: Medzihradszky
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Marco
authors.initials: M
authors.lastname: Terenzio
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Alber
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sandip
authors.initials: S
authors.lastname: Koley
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Albina
authors.initials: A
authors.lastname: Lin
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Rozenbaum
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Yudin
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Pabitra K
authors.initials: PK
authors.lastname: Sahoo
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gomes
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.affiliation: Tnuva, Bet Shean 11710, Israel.
authors.forename: Wasim
authors.initials: W
authors.lastname: Geraisy
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Huebner
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Yaron
authors.affiliation: Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Twiss
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: mike.fainzilber@weizmann.ac.il.
authors.forename: Mike
authors.initials: M
authors.lastname: Fainzilber
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D048429:Cell Size; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D055495:Neurogenesis; D010750:Phosphoproteins / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097796:Nucleolin