Developmentally-programmed FMRP expression in oligodendrocytes : a potential role of FMRP in regulating translation in oligodendroglia progenitors

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.

Medienart:

Artikel

Erscheinungsjahr:

2004

Erschienen:

2004

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Human molecular genetics - 13(2004), 1 vom: 01. Jan., Seite 79-89

Sprache:

Englisch

Beteiligte Personen:

Wang, Houping [VerfasserIn]
Ku, Li [VerfasserIn]
Osterhout, Donna J [VerfasserIn]
Li, Wen [VerfasserIn]
Ahmadian, Amir [VerfasserIn]
Liang, Zhe [VerfasserIn]
Feng, Yue [VerfasserIn]

Themen:

139135-51-6
Comparative Study
DNA Primers
FMR1 protein, human
Fragile X Mental Retardation Protein
Journal Article
Myelin Basic Protein
Nerve Tissue Proteins
RNA, Messenger
RNA-Binding Proteins
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Anmerkungen:

Date Completed 10.08.2004

Date Revised 15.11.2012

published: Print-Electronic

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM143320033