Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Nat Commun. 2018 Feb 8;9(1):586. doi: 10.1038/s41467-018-02874-0.
Telomerase is a reverse transcriptase complex that ensures stable maintenance of linear eukaryotic chromosome ends by overcoming the end replication problem, posed by the inability of replicative DNA polymerases to fully replicate linear DNA. The catalytic subunit TERT must be assembled properly with its telomerase RNA for telomerase to function, and studies in Tetrahymena have established that p65, a La-related protein 7 (LARP7) family protein, utilizes its C-terminal xRRM domain to promote assembly of the telomerase ribonucleoprotein (RNP) complex. However, LARP7-dependent telomerase complex assembly has been considered as unique to ciliates that utilize RNA polymerase III to transcribe telomerase RNA. Here we show evidence that fission yeast Schizosaccharomyces pombe utilizes the p65-related protein Pof8 and its xRRM domain to promote assembly of RNA polymerase II-encoded telomerase RNA with TERT. Furthermore, we show that Pof8 contributes to repression of the transcription of noncoding RNAs at telomeres.
端粒酶是一种逆转录酶复合物，通过克服复制性 DNA 聚合酶无法完全复制线性 DNA 所带来的末端复制问题，确保线性真核染色体末端的稳定维持。端粒酶的催化亚基 TERT 必须与其端粒酶 RNA 正确组装，才能发挥作用，而 Tetrahymena 的研究已经确立，p65（一种 La 相关蛋白 7 [LARP7] 家族蛋白）利用其 C 端 xRRM 结构域促进端粒酶核糖核蛋白（RNP）复合物的组装。然而，LARP7 依赖性端粒酶复合物组装被认为是纤毛类动物所特有的，纤毛类动物利用 RNA 聚合酶 III 转录端粒酶 RNA。在这里，我们提供的证据表明，裂殖酵母 Schizosaccharomyces pombe 利用 p65 相关蛋白 Pof8 及其 xRRM 结构域促进 RNA 聚合酶 II 编码的端粒酶 RNA 与 TERT 的组装。此外，我们还表明，Pof8 有助于抑制端粒处非编码 RNA 的转录。
