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PMID:14613971

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Citation

Wang, H, Ku, L, Osterhout, DJ, Li, W, Ahmadian, A, Liang, Z and Feng, Y (2004) Developmentally-programmed FMRP expression in oligodendrocytes: a potential role of FMRP in regulating translation in oligodendroglia progenitors. Hum. Mol. Genet. 13:79-89

Abstract

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.

Links

PubMed Online version:10.1093/hmg/ddh009

Keywords

Brain/embryology; Brain/metabolism; Cell Line; DNA Primers; Fragile X Mental Retardation Protein; Gene Expression Regulation, Developmental; Humans; Immunoblotting; Myelin Basic Protein/genetics; Myelin Basic Protein/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Oligodendroglia/metabolism; Plasmids/genetics; Precipitin Tests; Protein Binding; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Binding Proteins; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FMR1

located_in

GO:0043204: perikaryon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:FMR1

located_in

GO:0043204: perikaryon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:FMR1

located_in

GO:0097386: glial cell projection

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:FMR1

part_of

GO:0005844: polysome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FMR1

enables

GO:0003730: mRNA 3'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FMR1

part_of

GO:0005844: polysome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FMR1

part_of

GO:0043204: perikaryon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FMR1

involved_in

GO:0017148: negative regulation of translation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

enables

GO:0003729: mRNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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