Jansson Linnea I, Akiyama Ben M, Ooms Alexandra, Lu Cheng, Rubin Seth M, Stone Michael D
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, USA.
Department of Chemistry and Molecular Genetics, University of Colorado School of Medicine, Denver, Colorado, USA.
Nat Struct Mol Biol. 2015 Nov;22(11):883-8. doi: 10.1038/nsmb.3101. Epub 2015 Oct 5.
Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-Å crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides.
端粒酶对于维持染色体末端富含鸟嘌呤的重复端粒DNA序列至关重要。为此，端粒酶逆转录酶（TERT）亚基反复使用完整端粒酶RNA（TER）的一个小区域作为模板。端粒酶催化的一个基本特征是对模板边界进行严格定义，以确定TERT逆转录的精确TER核苷酸。我们报道了与TER的模板边界元件（TBE）结合的嗜热四膜虫TERT RNA结合结构域（tTRBD）的3埃晶体结构。tTRBD楔入TBE RNA茎环的基部，每条侧翼RNA链围绕蛋白质结构域的相对两侧缠绕。该结构说明了tTRBD如何通过将TBE定位在距TERT活性位点正确的距离来建立模板边界，从而阻止非模板核苷酸的复制。
