G-Quadruplex DNA- and RNA-Specific-Binding Proteins Engineered from the RGG Domain of TLS/FUS

ACS Chem Biol. 2015 Nov 20;10(11):2564-9. doi: 10.1021/acschembio.5b00566. Epub 2015 Sep 21.

Abstract

Human telomere DNA (Htelo) and telomeric repeat-containing RNA (TERRA) are integral telomere components containing the short DNA repeats d(TTAGGG) and RNA repeats r(UUAGGG), respectively. Htelo and TERRA form G-quadruplexes, but the biological significance of their G-quadruplex formation in telomeres is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful for understanding the functions of each G-quadruplex. Here we report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of Htelo and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G-quadruplexes of Htelo and TERRA have distinct functions in telomere histone methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry
  • Arginine / genetics
  • Circular Dichroism
  • DNA / chemistry
  • Electrophoretic Mobility Shift Assay
  • G-Quadruplexes*
  • Glycine / chemistry
  • Glycine / genetics
  • HeLa Cells
  • Humans
  • Protein Engineering*
  • Protein Structure, Tertiary / genetics
  • RNA / chemistry
  • RNA-Binding Proteins / chemical synthesis*
  • RNA-Binding Proteins / chemistry
  • Repetitive Sequences, Nucleic Acid / genetics

Substances

  • RNA-Binding Proteins
  • RNA
  • DNA
  • Arginine
  • Glycine