Human Molecular Genetics Advance Access originally published online on November 12, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Molecular Genetics, 2004, Vol. 13, No. 1 79-89
DOI: 10.1093/hmg/ddh009
© 2004 Oxford University Press
Developmentally-programmed FMRP expression in oligodendrocytes: a potential role of FMRP in regulating translation in oligodendroglia progenitors
1Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA and 2Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, NY, USA
Received August 18, 2003; Revised October 29, 2003; Accepted November 3, 2003
The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein whose function is implicated in regulating protein synthesis of its mRNA targets. The lack of FMRP leads to abnormal synapse development in the brain and impaired learning/memory. Although FMRP is predominantly expressed in neurons of the adult brain, whether FMRP also functions in glia during early development remains elusive, since expression of FMRP in glia has not been rigorously examined. This is an important question because recent studies revealed important roles of glia in synaptic development. Here we report that in addition to the observed neuronal expression, FMRP expression is detected in oligodendroglia progenitor cells (OPCs), immature oligodendrocytes and oligodendroglia cell lines, where it interacts with a subgroup of oligodendrocyte-specific mRNAs, including the myelin basic protein (MBP) mRNA. FMRP expression gradually declines as oligodendrocytes differentiate in vitro and in the developing brain. The decline of FMRP expression during oligodendrocyte differentiation is associated with a vigorous up-regulation of the MBP protein. In addition, we show that the MBP 3'untranslated region (3'UTR) is necessary and sufficient for binding FMRP, and mediates translation inhibition of a reporter gene by FMRP specifically in oligodendrocytes. These results support the hypothesis that FMRP may participate in regulating translation of its bound mRNAs in oligodendroglia during early brain development.
* To whom correspondence should be addressed at: Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. Tel: +1 4047270351; Fax: +1 4047270365; Email: yfeng{at}emory.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Bureau, G. M. G. Shepherd, and K. Svoboda Circuit and Plasticity Defects in the Developing Somatosensory Cortex of Fmr1 Knock-Out Mice J. Neurosci., May 14, 2008; 28(20): 5178 - 5188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Tessier and K. Broadie Drosophila fragile X mental retardation protein developmentally regulates activity-dependent axon pruning Development, April 15, 2008; 135(8): 1547 - 1557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, J. B. Dictenberg, L. Ku, W. Li, G. J. Bassell, and Y. Feng Dynamic Association of the Fragile X Mental Retardation Protein as a Messenger Ribonucleoprotein between Microtubules and Polyribosomes Mol. Biol. Cell, January 1, 2008; 19(1): 105 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhao, L. Ku, Y. Chen, M. Xia, P. LoPresti, and Y. Feng QKI Binds MAP1B mRNA and Enhances MAP1B Expression during Oligodendrocyte Development Mol. Biol. Cell, October 1, 2006; 17(10): 4179 - 4186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lu, H. Wang, Z. Liang, L. Ku, W. T. O'Donnell, W. Li, S. T. Warren, and Y. Feng The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development PNAS, October 19, 2004; 101(42): 15201 - 15206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Smith, B. Coffee, and D. Reines Occupancy and synergistic activation of the FMR1 promoter by Nrf-1 and Sp1 in vivo Hum. Mol. Genet., August 1, 2004; 13(15): 1611 - 1621. [Abstract] [Full Text] [PDF]
|
|