The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein

Philip J. Young, Jonathan W. Francis, Diane Lince, Keith Coon, Elliot Androphy, Christian L. Lorson

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The survival motor neuron (SMN) gene is the spinal muscular atrophy (SMA) determining gene. Here we report that the SMN protein product interacts in vitro and in vivo with the arginine/glycine (RG)-rich RNA binding protein and transcription factor, Ewing's sarcoma (EWS). Recently, the SMN encoded Tudor domain (exon 3) and the YG-motifs (exon 6) have been shown to be involved in binding to RG-rich proteins. Here, we demonstrate that the Tudor domain encoded by SMN exon 3 is independently sufficient to mediate the interaction with EWS. Synthetic mutations within the Tudor domain, as well as a SMA patient-derived mutation within exon 3, reduced the levels of the SMN/EWS interaction. Carboxyl-terminal SMN mutations that prevent formation of SMN oligomers also indirectly reduced EWS binding. A role for arginine methylation has been observed in some RG-containing SMN-interacting proteins. Here we demonstrate that SMN interacts with non-methylated EWS and an EWS-derived RG-containing peptide. In contrast to previously reported results, symmetrical dimethylation of the EWS-derived RG-peptide results in a quantitative increase in the dissociation rate between SMN and the symmetrical dimethylated EWS RG-peptide. Consistent with the interaction data, endogenous and transiently expressed SMN co-localizes with endogenous EWS in a number of cultured cell lines, as well as rat primary neuron cultures. Anti-sense RNA experiments, however, demonstrate that EWS does not mediate the nuclear distribution of SMN or other Cajal body components.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalMolecular Brain Research
Volume119
Issue number1
DOIs
StatePublished - Nov 6 2003
Externally publishedYes

Fingerprint

Ewing's Sarcoma
Motor Neurons
Proteins
Exons
Spinal Muscular Atrophy
Peptides
Mutation
Arginine
Tudor Domain
Antisense RNA
RNA-Binding Proteins
Glycine
Methylation
Genes
Cultured Cells
Transcription Factors
Survival Rate

Keywords

  • Arginine/ glycine domain
  • Ewing's sarcoma
  • Spinal muscular atrophy
  • Surface plasmon resonance
  • Survival motor neuron
  • Tudor domain

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein. / Young, Philip J.; Francis, Jonathan W.; Lince, Diane; Coon, Keith; Androphy, Elliot; Lorson, Christian L.

In: Molecular Brain Research, Vol. 119, No. 1, 06.11.2003, p. 37-49.

Research output: Contribution to journalArticle

Young, Philip J. ; Francis, Jonathan W. ; Lince, Diane ; Coon, Keith ; Androphy, Elliot ; Lorson, Christian L. / The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein. In: Molecular Brain Research. 2003 ; Vol. 119, No. 1. pp. 37-49.
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