An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage
An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage
复制标题
DOI：
10.1101/gad.202960.112
复制
发表时间：
2012-11-15
影响因子：
10.5
通讯作者：
Shippen, Dorothy E.
中科院分区：
文献类型：
--
作者：
Cifuentes-Rojas, Catherine;Nelson, Andrew D. L.;Shippen, Dorothy E.
端粒酶通过重复复制其RNA模板TER来补充端粒。与其他模式生物不同，拟南芥含有两个不同的基因。然而，端粒维持只需要TER1。这里我们来研究一下TER2的功能。我们发现，TER2在体内是剪接的，其3‘端被截断以产生第三种TER异构体，TER2(S)。TERT优先与TER2&>TER1&>TER2关联(S)。此外，TER2和TER2(S)与Ku和POT1b(端粒保护)组装，形成有别于TER1RNP的核糖核蛋白(RNP)复合体。TER2缺失的植物表现出端粒酶活性增加，而TER2过表达则抑制TER1合成端粒并导致端粒缩短。这些发现认为，TER2通过将TERT隔离在非生产的RNP复合体中来负向调节端粒酶。玉米素引入DNA双链断裂导致TER2立即和特异的尖峰，并伴随着端粒酶活性的下降。这种反应不是由复制压力或端粒功能障碍触发的，在ter2突变体中被取消。我们的结论是，拟南芥端粒酶是由TER2调控的，TER2是一种新的DNA损伤诱导的非编码RNA，它与规范的TER协同工作，促进基因组的完整性。
Telomerase replenishes telomere tracts by reiteratively copying its RNA template, TER. Unlike other model organisms, Arabidopsis thaliana harbors two divergent TER genes. However, only TER1 is required for telomere maintenance. Here we examine the function of TER2. We show that TER2 is spliced and its 3'end is truncated in vivo to generate a third TER isoform, TER2(S). TERT preferentially associates with TER2 > TER1 > TER2(S). Moreover, TER2 and TER2(S) assemble with Ku and POT1b (protection of telomeres), forming RNP (ribonucleoprotein) complexes distinct from TER1 RNP. Plants null for TER2 display increased telomerase enzyme activity, while TER2 overexpression inhibits telomere synthesis from TER1 and leads to telomere shortening. These findings argue that TER2 negatively regulates telomerase by sequestering TERT in a nonproductive RNP complex. Introduction of DNA double-strand breaks by zeocin leads to an immediate and specific spike in TER2 and a concomitant decrease in telomerase enzyme activity. This response is not triggered by replication stress or telomere dysfunction and is abrogated in ter2 mutants. We conclude that Arabidopsis telomerase is modulated by TER2, a novel DNA damage-induced noncoding RNA that works in concert with the canonical TER to promote genome integrity.