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J. Biol. Chem., Vol. 282, Issue 26, 18857-18863, June 29, 2007

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Functional Characterization of Yeast Telomerase RNA Dimerization^*

From the Department of Pathology and Laboratory Medicine, Experimental Pathology Division, Emory University School of Medicine, Atlanta, Georgia 30322

Telomerase is the cellular RNA-dependent DNA polymerase (i.e. reverse transcriptase) that uses an integral RNA template to synthesize telomeric DNA repeats at the ends of linear chromosomes. Human telomerase RNA (hTERC) is thought to function as a dimeric complex consisting of two RNAs that interact with each other physically as well as genetically. We show here for the first time that the yeast Saccharomyces cerevisiae telomerase RNA TLC1 likewise forms dimers in vitro. TLC1 dimerization depends on a unique 6-base self-complementary sequence, which closely mimics palindromic sequences that mediate functional dimerization of HIV-1 and other retroviral genomes. We found that dissimilar but comparably located TLC1 palindromes from other sensu stricto yeasts can functionally substitute for that of S. cerevisiae. Yeast cells expressing dimerization-defective TLC1 alleles have shorter telomeres than those with wild-type TLC1. This study, therefore, highlights dimerization as a functionally conserved feature of the RNA templates utilized by reverse transcriptases of both viral and cellular origins.

Received for publication, January 3, 2007 , and in revised form, May 8, 2007.

^* This study was supported by funds from the Leukemia & Lymphoma Society of America and the American Cancer Society (to H. L.) and by National Institutes of Health Grant AI-40317 (to T. G. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Pathology & Laboratory Medicine, Emory University School of Medicine, 615 Michael St., Whitehead Bldg., Rm. 105L, Atlanta, GA 30322. Tel.: 404-712-2841; Fax: 404-727-8538; E-mail: hly{at}emory.edu.

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