Identification of Ewing's sarcoma protein as a G-quadruplex DNA- and RNA-binding protein.

Kentaro Takahama, Katsuhito Kino, Shigeki Arai, Riki Kurokawa, Takanori Oyoshi

Department of Chemistry, Faculty of Science, Shizuoka University, Japan.

The FEBS journal 2011 Apr

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The Ewing's sarcoma (EWS) oncogene contains an N-terminal transcription activation domain and a C-terminal RNA-binding domain. Although the EWS activation domain is a potent transactivation domain that is required for the oncogenic activity of several EWS fusion proteins, the normal role of intact EWS is poorly characterized because little is known about its nucleic acid recognition specificity. Here we show that the Arg-Gly-Gly (RGG) domain of the C-terminal in EWS binds to the G-rich single-stranded DNA and RNA fold in the G-quadruplex structure. Furthermore, inhibition of DNA polymerase on a template containing a human telomere sequence in the presence of RGG occurs in an RGG concentration-dependent manner by the formation of a stabilized G-quadruplex DNA-RGG complex. In addition, mutated RGG containing Lys residues replacing Arg residues at specific Arg-Gly-Gly sites and RGG containing Arg methylated by protein arginine N-methyltransferase 3 decrease the binding ability of EWS to G-quadruplex DNA and RNA. These findings suggest that the RGG of EWS binds to G-quadruplex DNA and RNA via the Arg residues in it. © 2011 The Authors Journal compilation © 2011 FEBS.

Citation

Kentaro Takahama, Katsuhito Kino, Shigeki Arai, Riki Kurokawa, Takanori Oyoshi. Identification of Ewing's sarcoma protein as a G-quadruplex DNA- and RNA-binding protein. The FEBS journal. 2011 Apr;278(6):988-98