Elsevier

Neurobiology of Disease

Volume 7, Issue 4, August 2000, Pages 416-428
Neurobiology of Disease

Regular Article
Translational Control of Ribosomal Protein L4 mRNA Is Required for Rapid Neurite Regeneration

https://doi.org/10.1006/nbdi.2000.0293Get rights and content

Abstract

Under some circumstances neurons can be primed to rapidly regenerate injured neuritic processes independent of new gene expression. Such transcription-independent neurite extension occurs in adult rat sensory neurons cultured after sciatic nerve crush and in NGF-differentiated PC12 cells whose neurites have been mechanically sheared. In the PC12 cells, neurite regeneration occurs by means of translational control of mRNAs which were transcribed prior to neurite injury. The survival of such translationally regulated mRNAs is relatively short in the differentiated PC12 cells (≤10 h). By subtractive hybridization, we have isolated a short-lived mRNA from differentiated PC12 cells. This mRNA, which encodes the ribosomal protein L4, is translationally regulated during neurite regeneration in PC12 cells. Antisense oligonucleotides to L4 mRNA inhibit neurite regeneration from the differentiated PC12 cells as well as axonal elongation from conditioned sensory neurons, indicating that ongoing translation of L4 mRNA is needed for these forms of rapid transcription-independent neurite growth. Taken together, these data point to the importance of translational regulation of existing neuronal mRNAs in the regenerative responses to neuronal injury. Although there are other examples of neuronal translational control, there are no other known neuronal proteins whose levels are regulated predominantly by translational rather than transcriptional control.

References (69)

  • P. Chomczynski et al.

    Single-step method of RNA isolation by guanidine isothiocyanate–phenol–chloroform extraction

    Anal. Biochem.

    (1987)
  • H. Dong et al.

    Ribosome mutants with altered accuracy translate with reduced processivity

    J. Mol. Biol.

    (1995)
  • D.S. Forman et al.

    Time course of the condition lesion effect on axonal regeneration

    Brain Res.

    (1980)
  • H.B. Jefferies et al.

    Elongation factor-1 alpha mRNA is selectively translated following mitogenic stimulation

    J. Biol. Chem.

    (1994)
  • H. Kang et al.

    Neurotrophin-induced modulation of synaptic transmission in the adult hippocampus

    J. Physiol. Paris

    (1995)
  • M. Krug et al.

    Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats

    Brain Res. Bull.

    (1984)
  • I.G. McQuarrie

    The effect of a conditioning lesion on the regeneration of motor axons

    Brain Res.

    (1978)
  • I.G. McQuarrie et al.

    Effect of condition lesion on optic nerve regeneration in goldfish

    Brain Res.

    (1981)
  • P.P. Mueller et al.

    A ribosomal protein is required for translational regulation of GCN4 mRNA. Evidence for involvement of the ribosome in eIF2 recycling

    J. Biol. Chem.

    (1998)
  • S. Neumann et al.

    Regeneration of dorsal column fibers into and beyond lesion site following adult spinal cord injury

    Neuron

    (1999)
  • S. Otani et al.

    Maintenance of long-term potentiation requires protein synthesis but not messenger RNA synthesis immediately post-tetanization

    Neuroscience

    (1989)
  • L. Pellizzoni et al.

    A Xenopus laevis homologue of the La autoantigen binds the pyrimidine tract of the 5′ UTR of ribosomal protein mRNAs in vitro: Implication of a protein factor in complex formation

    J. Mol. Biol.

    (1996)
  • L. Pellizzoni et al.

    Cellular nucleic acid binding protein binds a conserved region of the 5′UTR of Xenopus laevis ribosomal protein mRNAs

    J. Mol. Biol.

    (1997)
  • L. Pellizzoni et al.

    Involvement of the Xenopus laevis Ro60 autoantigen in the alternative interaction of La and CNBP proteins with the 5′UTR of L4 ribosomal protein mRNA

    J. Mol. Biol.

    (1998)
  • P. Pierandrei-Amaldi et al.

    Expression of ribosomal-protein genes in Xenopus laevis development

    Cell

    (1982)
  • C. Presutti et al.

    Ribosomal protein L2 in Saccharomyces cerevisiae is homologous to ribosomal protein L1 in Xenopus laevis: Isolation and characterization of the genes

    J. Biol. Chem.

    (1988)
  • G. Thomas et al.

    TOR signalling and control of cell growth

    Curr. Opin. Cell Biol.

    (1997)
  • I.J. Weiler et al.

    Synapse-activated protein synthesis as a possible mechanism of plastic neural change

    Prog. Brain Res.

    (1994)
  • I.G. Wool

    Extraribosomal functions of ribosomal proteins

    Trends Biochem. Sci.

    (1996)
  • G.R. Al-Atia et al.

    Translational regulation of mRNAs for ribosomal proteins during early Drosophilia development

    Biochemistry

    (1985)
  • R. Aloni et al.

    Selective translational control and non-specific posttranscriptional regulation of ribosomal protein gene expression during development and regeneration of rat liver

    Mol. Cell. Biol.

    (1992)
  • F. Amaldi et al.

    TOP genes: A translationally controlled class of genes including those coding for ribosomal proteins

    Prog. Mol. Subcell. Biol.

    (1997)
  • J.E. Arrand

    Preparation of nucleic acid probes

  • D. Avni et al.

    Vertebrate mRNAs with a 5′-terminal pyrimidine tract are candidates for translational repression in quiescent cells: Characterization of the translational cis-regulatory element

    Mol. Cell. Biol.

    (1994)
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