Nucleic Acids Research Advance Access originally published online on October 25, 2008
Nucleic Acids Research 2008 36(21):6816-6824; doi:10.1093/nar/gkn767
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Nucleic Acids Research, 2008, Vol. 36, No. 21 6816-6824
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Elucidation of the mode of interaction in the UP1–telomerase RNA–telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity
1Supramolecular Biology, International Graduate School of Arts and Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, 2Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, 79–7 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, 3Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 and 4PRESTO, JST, Japan
*To whom correspondence should be addressed. Tel: +81 45 508 7213; Fax: +81 45 508 7361; Email: katahira{at}tsurumi.yokohama-cu.ac.jp
Received August 6, 2008. Revised October 7, 2008. Accepted October 7, 2008.
We found that UP1, a proteolytic product of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), both enhances and represses the telomerase activity. The formation of the UP1–telomerase RNA–telomeric DNA ternary complex was revealed by a gel retardation experiment. The interactions in the ternary and binary complexes were elucidated by NMR. UP1 has two nucleic acid-binding domains, BD1 and BD2. In the UP1–telomerase RNA binary complex, both BD1 and BD2 interact with telomerase RNA. Interestingly, when telomeric DNA was added to the binary complex, telomeric DNA bound to BD1 in place of telomerase RNA. Thus, BD1 basically binds to telomeric DNA, while BD2 mainly binds to telomerase RNA, which resulted in the formation of the ternary complex. Here, UP1 bridges telomerase and telomeric DNA. It is supposed that UP1/hnRNP A1 serves to recruit telomerase to telomeric DNA through the formation of the ternary complex. A model has been proposed for how hnRNP A1/UP1 contributes to enhancement of the telomerase activity through recruitment and unfolding of the quadruplex of telomeric DNA.