Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095-1569, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095-1569, USA.
Curr Opin Struct Biol. 2022 Oct;76:102446. doi: 10.1016/j.sbi.2022.102446. Epub 2022 Sep 6.
Telomerase is an RNA-protein complex comprising telomerase reverse transcriptase, a non-coding telomerase RNA, and proteins involved in biogenesis, assembly, localization, or recruitment. Telomerase synthesizes the telomeric DNA at the 3'-ends of linear chromosomes. During the past decade, structural studies have defined the architecture of Tetrahymena and human telomerase as well as protein and RNA domain structures, but high-resolution details of interactions remained largely elusive. In the past two years, several sub-4 Å cryo-electron microscopy structures of telomerase were published, including Tetrahymena telomerase at different steps of telomere repeat addition and human telomerase with telomere shelterin proteins that recruit telomerase to telomeres. These and other recent structural studies have expanded our understanding of telomerase assembly, mechanism, recruitment, and mutations leading to disease.
端粒酶是一种 RNA-蛋白复合物,由端粒酶逆转录酶、非编码端粒酶 RNA 和参与生物发生、组装、定位或募集的蛋白质组成。端粒酶在线性染色体的 3'末端合成端粒 DNA。在过去的十年中,结构研究已经定义了四膜虫和人端粒酶的结构以及蛋白质和 RNA 结构域结构,但相互作用的高分辨率细节在很大程度上仍然难以捉摸。在过去的两年中,发表了几个亚 4 Å 的端粒酶冷冻电子显微镜结构,包括处于端粒重复添加不同步骤的四膜虫端粒酶和与招募端粒酶到端粒的端粒庇护蛋白结合的人端粒酶。这些和其他最近的结构研究扩展了我们对端粒酶组装、机制、募集和导致疾病的突变的理解。
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