Functional characterization of yeast telomerase RNA dimerization
Functional characterization of yeast telomerase RNA dimerization
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DOI：
10.1074/jbc.m700057200
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发表时间：
2007-06-29
影响因子：
4.8
通讯作者：
Ly, Hinh
中科院分区：
文献类型：
--
作者：
Gipson, Clay L.;Xin, Zhong-Tao;Ly, Hinh
端粒酶是细胞内依赖于RNA的DNA聚合酶(即逆转录酶)，它使用完整的RNA模板在线性染色体末端合成端粒DNA重复序列。人类端粒酶RNA(HTERC)被认为是由两个在物理上和基因上相互作用的RNA组成的二聚体复合体。我们在这里首次展示了酵母酿酒酵母端粒酶RNA TLC1在体外类似地形成二聚体。TLC1的二聚化依赖于一个独特的6碱基自互补序列，它与介导HIV-1和其他逆转录病毒基因组功能二聚化的回文序列非常相似。我们发现，与其他感官酵母不同但位置相似的TLC1回文可以在功能上取代酿酒酵母的回文。表达二聚化缺陷TLC1等位基因的酵母细胞的端粒比野生型TLC1的酵母细胞短。因此，这项研究强调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的特征。
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.