Telomerase RNA processing: implications for human health and disease,STEM CELLS

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Telomerase RNA processing: implications for human health and disease
STEM CELLS ( IF 4.0 ) Pub Date : 2020-09-01 , DOI: 10.1002/stem.3270
Neha Nagpal _{1,

2,

3,

4} , Suneet Agarwal _{1,

2,

3,

4}

Affiliation

Telomeres are composed of repetitive DNA sequences that are replenished by the enzyme telomerase to maintain the self‐renewal capacity of stem cells. The RNA component of human telomerase (TERC) is the essential template for repeat addition by the telomerase reverse transcriptase (TERT), and also serves as a scaffold for several factors comprising the telomerase ribonucleoprotein (RNP). Unique features of TERC regulation and function have been informed not only through biochemical studies but also through human genetics. Disease‐causing mutations impact TERC biogenesis at several levels including RNA transcription, post‐transcriptional processing, folding, RNP assembly, and trafficking. Defects in TERC reduce telomerase activity and impair telomere maintenance, thereby causing a spectrum of degenerative diseases called telomere biology disorders (TBDs). Deciphering mechanisms of TERC dysregulation have led to a broader understanding of noncoding RNA biology, and more recently points to new therapeutic strategies for TBDs. In this review, we summarize over two decades of work revealing mechanisms of human telomerase RNA biogenesis, and how its disruption causes human diseases.

中文翻译：

端粒酶 RNA 处理：对人类健康和疾病的影响

端粒由重复的 DNA 序列组成，由端粒酶补充，以维持干细胞的自我更新能力。人端粒酶 (TERC) 的 RNA 成分是端粒酶逆转录酶 (TERT) 重复添加的重要模板，并且还充当包括端粒酶核糖核蛋白 (RNP) 在内的多种因子的支架。 TERC 调节和功能的独特特征不仅通过生化研究而且通过人类遗传学了解。致病突变在多个层面影响 TERC 生物合成，包括 RNA 转录、转录后加工、折叠、RNP 组装和运输。 TERC 缺陷会降低端粒酶活性并损害端粒维持，从而导致一系列称为端粒生物学障碍 (TBD) 的退行性疾病。 TERC 失调机制的破译使人们对非编码 RNA 生物学有了更广泛的了解，最近还指出了 TBD 的新治疗策略。在这篇综述中，我们总结了二十多年的工作，揭示了人类端粒酶 RNA 生物合成的机制，以及它的破坏如何导致人类疾病。

更新日期：2020-09-01

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