Characterization of G-Quadruplex DNA- and RNA-Binding Protein

Abstract

Mammalian telomeres containing TTAGG repeats are bound by a multiprotein complex with a telomeric repeat-containing RNA (TERRA) containing UUAGGG repeats, which is a long noncoding RNA transcribed from the telomeres. Telomere DNA and TERRA form a G-quadruplex in vitro. The functions of the G-quadruplex structures in the telomere, however, are not clear, because little is known about G-quadruplex specific binding proteins and G-quadruplex RNA-binding molecules without binding to G-quadruplex telomere DNA. We have reported that the Arg-Glu-Gly motif in Translocated in Liposarcoma (TLS) forms G-quadruplex telomere DNA and TERRA simultaneously in vitro. Furthermore, TLS promotes the methylation of hinstone H4 and H3 at lysine and regulates telomere length. These finding suggest that the G-quadruplex functions as a scaffold for telomere-binding protein, TLS. Moreover, we have shown that substitution of Tyr for Phe in the RGG motif of TLS converts its binding specificity solely toward G-quadruplex TERRA. This molecule binds to loops within the G-quadruplexes of TERRA by recognizing the 2′-OH of the riboses. It will be useful for investigating biological roles of the G-quadruplex in long noncoding RNA.