Phosphorylation influences the translation state of FMRP-associated polyribosomes

Stephanie Ceman, William T. O'Donnell, Matt Reed, Stephana Patton, Jan Pohl, Stephen T. Warren

Research output: Contribution to journalArticle

Abstract

Fragile X mental retardation protein, FMRP, is absent in patients with fragile X syndrome, a common form of mental retardation. FMRP is a nucleocytoplasmic RNA binding protein that is primarily associated with polyribosomes. FMRP is believed to be a translational repressor and may regulate the translation of certain mRNAs at the base of dendritic spines in neurons. However, little is known about the regulation of FMRP. Using mass spectrometry and site-directed mutagenesis, we show that FMRP is phosphorylated between residues 483 and 521, N-terminal to the RGG box, both in murine brain and in cultured cells. Primary phosphorylation occurs on the highly conserved serine 499, which triggers hierarchical phosphorylation of nearby serines. FMRP is phosphorylated within 2-4 h of synthesis, however, phosphorylation has no effect on the half-life of the protein. In contrast to the Drosophila ortholog dFxr, the phosphorylation status of mammalian FMRP does not influence its association with specific mRNAs in vivo. However, we find unphosphorylated FMRP associated with actively translating polyribosomes while a fraction of phosphorylated FMRP is associated with apparently stalled polyribosomes. Our data suggest that the phosphorylation may regulate FMRP and that the release of FMRP-induced translational suppression may involve a dephosphorylation signal.

Original languageEnglish (US)
Pages (from-to)3295-3305
Number of pages11
JournalHuman molecular genetics
Volume12
Issue number24
DOIs
StatePublished - Dec 15 2003

Fingerprint

Polyribosomes
Phosphorylation
Serine
Fragile X Mental Retardation Protein
Fragile X Syndrome
Dendritic Spines
RNA-Binding Proteins
Protein Biosynthesis
Site-Directed Mutagenesis
Intellectual Disability
Drosophila
Half-Life
Cultured Cells
Mass Spectrometry
Neurons
Messenger RNA
Brain
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Ceman, S., O'Donnell, W. T., Reed, M., Patton, S., Pohl, J., & Warren, S. T. (2003). Phosphorylation influences the translation state of FMRP-associated polyribosomes. Human molecular genetics, 12(24), 3295-3305. https://doi.org/10.1093/hmg/ddg350

Phosphorylation influences the translation state of FMRP-associated polyribosomes. / Ceman, Stephanie; O'Donnell, William T.; Reed, Matt; Patton, Stephana; Pohl, Jan; Warren, Stephen T.

In: Human molecular genetics, Vol. 12, No. 24, 15.12.2003, p. 3295-3305.

Research output: Contribution to journalArticle

Ceman, S, O'Donnell, WT, Reed, M, Patton, S, Pohl, J & Warren, ST 2003, 'Phosphorylation influences the translation state of FMRP-associated polyribosomes', Human molecular genetics, vol. 12, no. 24, pp. 3295-3305. https://doi.org/10.1093/hmg/ddg350
Ceman, Stephanie ; O'Donnell, William T. ; Reed, Matt ; Patton, Stephana ; Pohl, Jan ; Warren, Stephen T. / Phosphorylation influences the translation state of FMRP-associated polyribosomes. In: Human molecular genetics. 2003 ; Vol. 12, No. 24. pp. 3295-3305.
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