Proteomic analysis defines the interactome of telomerase in the protozoan parasite, Trypanosoma brucei.

Proteomic analysis defines the interactome of telomerase in the protozoan parasite, Trypanosoma brucei.
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蛋白质组学分析定义了原生动物寄生虫布氏锥虫中端粒酶的相互作用组。

DOI:
10.3389/fcell.2023.1110423
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发表时间:
2023
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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端粒酶是一种核糖核蛋白酶,负责维持染色体的端粒末端。端粒酶需要两个主要成分才能发挥作用:端粒酶逆转录酶(TERT)和为端粒DNA合成提供模板的端粒酶RNA(TR)。TR是一种非编码的长RNA,它构成了一个大的结构支架的基础,许多辅助蛋白可以在其上结合并形成完整的端粒酶全酶。这些辅助蛋白的相互作用是端粒酶活性和细胞内调节所必需的。TERT的相互作用伙伴已经在酵母、人类和四膜虫模型中得到了很好的研究,但在寄生原虫中还没有得到很好的研究,包括临床上相关的人类寄生虫。在这里,我们以原生动物布氏锥虫(T.brucei)为模型,利用基于质谱学的方法鉴定了布氏锥虫TbTERT(TbTERT)的相互作用组。我们确定了TbTERT的已知和未知相互作用因素,突出了布氏毛滴虫端粒酶生物学的独特特征。这些与TbTERT的独特相互作用表明,布鲁氏毛滴虫和其他真核生物在端粒维持方面存在机械上的差异。
Telomerase is a ribonucleoprotein enzyme responsible for maintaining the telomeric end of the chromosome. The telomerase enzyme requires two main components to function: the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), which provides the template for telomeric DNA synthesis. TR is a long non-coding RNA, which forms the basis of a large structural scaffold upon which many accessory proteins can bind and form the complete telomerase holoenzyme. These accessory protein interactions are required for telomerase activity and regulation inside cells. The interacting partners of TERT have been well studied in yeast, human, and Tetrahymena models, but not in parasitic protozoa, including clinically relevant human parasites. Here, using the protozoan parasite, Trypanosoma brucei (T. brucei) as a model, we have identified the interactome of T. brucei TERT (TbTERT) using a mass spectrometry-based approach. We identified previously known and unknown interacting factors of TbTERT, highlighting unique features of T. brucei telomerase biology. These unique interactions with TbTERT, suggest mechanistic differences in telomere maintenance between T. brucei and other eukaryotes.
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