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

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• 作者：Kentaro Takahama ; Arisa Miyawaki ; Takumi Shitara ; Keita Mitsuya ; Masayuki Morikawa ; Masaki Hagihara ; Katsuhito Kino ; Ayumu Yamamoto ; Takanori Oyoshi
• 刊名：ACS Chemical Biology
• 出版年：2015
• 出版时间：November 20, 2015
• 年：2015
• 卷：10
• 期：11
• 页码：2564-2569
• 全文大小：364K
• ISSN：1554-8937

文摘

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.