Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Applied Cancer Research Pavillion, 3201 rue Jean-Mignault, Sherbrooke, Quebec, J1E 4K8, Canada.
J Mol Biol. 2017 Oct 27;429(21):3242-3254. doi: 10.1016/j.jmb.2017.01.013. Epub 2017 Jan 20.
Telomerase reverse transcriptase elongates telomeres to overcome their natural attrition and allow unlimited cellular proliferation, a characteristic shared by stem cells and the majority of malignant cancerous cells. The telomerase holoenzyme comprises a core RNA molecule, a catalytic protein subunit, and other accessory proteins. Malfunction of certain telomerase components can cause serious genetic disorders including dyskeratosis congenita and aplastic anaemia. A hierarchy of tightly regulated steps constitutes the process of telomerase biogenesis, which, if interrupted or misregulated, can impede the production of a functional enzyme and severely affect telomere maintenance. Here, we take a closer look at the budding yeast telomerase RNA component, TLC1, in its long lifetime journey around the cell. We review the extensive knowledge on TLC1 transcription and processing. We focus on exciting recent studies on telomerase assembly, trafficking, and nuclear dynamics, which for the first time unveil striking similarities between the yeast and human telomerase ribonucleoproteins. Finally, we identify questions yet to be answered and new directions to be followed, which, in the future, might improve our knowledge of telomerase biology and trigger the development of new therapies against cancer and other telomerase-related diseases.
端粒酶逆转录酶延长端粒以克服其自然损耗，从而实现无限的细胞增殖，这是干细胞和大多数恶性癌细胞的共同特征。端粒酶全酶由核心 RNA 分子、催化蛋白亚基和其他辅助蛋白组成。某些端粒酶成分的功能障碍会导致严重的遗传疾病，包括先天性角化不良和再生障碍性贫血。端粒酶生物发生的过程由一系列严格调控的步骤构成，如果这些步骤被中断或失调，可能会阻碍功能性酶的产生，并严重影响端粒的维持。在这里，我们仔细研究了 budding yeast 端粒酶 RNA 成分 TLC1 在细胞中的长期生命周期。我们回顾了关于 TLC1 转录和加工的广泛知识。我们专注于最近关于端粒酶组装、运输和核动态的令人兴奋的研究，这些研究首次揭示了酵母和人类端粒酶核糖核蛋白之间惊人的相似性。最后，我们确定了尚未回答的问题和有待探索的新方向，这些问题和方向可能会提高我们对端粒酶生物学的认识，并引发针对癌症和其他与端粒酶相关疾病的新疗法的开发。
