Gipson Clay L, Xin Zhong-Tao, Danzy Shamika C, Parslow Tristram G, Ly Hinh
Department of Pathology and Laboratory Medicine, Experimental Pathology Division, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Biol Chem. 2007 Jun 29;282(26):18857-63. doi: 10.1074/jbc.M700057200. Epub 2007 May 9.
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.
端粒酶是一种细胞内依赖RNA的DNA聚合酶（即逆转录酶），它利用一个整合的RNA模板在线性染色体末端合成端粒DNA重复序列。人端粒酶RNA（hTERC）被认为作为一种由两个RNA组成的二聚体复合物发挥作用，这两个RNA在物理和遗传上相互作用。我们在此首次表明，酿酒酵母端粒酶RNA TLC1在体外同样形成二聚体。TLC1二聚化依赖于一个独特的6碱基自我互补序列，该序列与介导HIV-1和其他逆转录病毒基因组功能二聚化的回文序列极为相似。我们发现，来自其他狭义酵母的不同但位置相当的TLC1回文序列可在功能上替代酿酒酵母的TLC1回文序列。表达二聚化缺陷型TLC1等位基因的酵母细胞的端粒比具有野生型TLC1的酵母细胞的端粒短。因此，这项研究突出了二聚化是病毒和细胞来源的逆转录酶所利用的RNA模板的一个功能保守特征。
