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进化和生化分析揭示芸薹科端粒酶核糖核蛋白复合物的保守性。

Evolutionary and biochemical analyses reveal conservation of the Brassicaceae telomerase ribonucleoprotein complex.

机构信息

School of Plant Sciences, University of Arizona, Tucson, Arizona, United States of America.

出版信息

PLoS One. 2020 Apr 9;15(4):e0222687. doi: 10.1371/journal.pone.0222687. eCollection 2020.

Abstract

The telomerase ribonucleoprotein complex (RNP) is essential for genome stability and performs this role through the addition of repetitive DNA to the ends of chromosomes. The telomerase enzyme is composed of a reverse transcriptase (TERT), which utilizes a template domain in an RNA subunit (TER) to reiteratively add telomeric DNA at the ends of chromosomes. Multiple TERs have been identified in the model plant Arabidopsis thaliana. Here we combine a phylogenetic and biochemical approach to understand how the telomerase RNP has evolved in Brassicaceae, the family that includes A. thaliana. Because of the complex phylogenetic pattern of template domain loss and alteration at the previously characterized A. thaliana TER loci, TER1 and TER2, across the plant family Brassicaceae, we bred double mutants from plants with a template deletion at AtTER1 and T-DNA insertion at AtTER2. These double mutants exhibited no telomere length deficiency, a definitive indication that neither of these loci encode a functional telomerase RNA. Moreover, we determined that the telomerase components TERT, Dyskerin, and the KU heterodimer are under strong purifying selection, consistent with the idea that the TER with which they interact is also conserved. To test this hypothesis further, we analyzed the substrate specificity of telomerase from species across Brassicaceae and determined that telomerase from close relatives bind and extend substrates in a similar manner, supporting the idea that TERs in different species are highly similar to one another and are likely encoded from an orthologous locus. Lastly, TERT proteins from across Brassicaceae were able to complement loss of function tert mutants in vivo, indicating TERTs from other species have the ability to recognize the native TER of A. thaliana. Finally, we immunoprecipitated the telomerase complex and identified associated RNAs via RNA-seq. Using our evolutionary data we constrained our analyses to conserved RNAs within Brassicaceae that contained a template domain. These analyses revealed a highly expressed locus whose disruption by a T-DNA resulted in a telomeric phenotype similar to the loss of other telomerase core proteins, indicating that the RNA has an important function in telomere maintenance.

摘要

端粒酶核糖核蛋白复合物(RNP)对于基因组稳定性至关重要,它通过在染色体末端添加重复 DNA 来发挥此作用。端粒酶由逆转录酶(TERT)组成,该酶利用 RNA 亚基(TER)中的模板结构域重复地在染色体末端添加端粒 DNA。在模式植物拟南芥中已经鉴定出多种 TER。在这里,我们结合系统发育和生化方法来了解端粒酶 RNP 在包括拟南芥在内的芸薹科植物中的进化情况。由于在之前表征的拟南芥 TER 基因座(TER1 和 TER2)中,模板结构域缺失和改变的复杂系统发育模式,以及在整个芸薹科植物家族中,我们从 AtTER1 模板缺失的植物和 AtTER2 的 T-DNA 插入的植物中培育出双突变体。这些双突变体没有表现出端粒长度不足,这明确表明这些基因座都不编码功能齐全的端粒酶 RNA。此外,我们确定端粒酶成分 TERT、Dyskerin 和 KU 异二聚体受到强烈的纯化选择,这与它们相互作用的 TER 也保守的观点一致。为了进一步验证这一假设,我们分析了来自芸薹科的不同物种的端粒酶的底物特异性,并确定亲缘关系密切的物种的端粒酶以相似的方式结合和延伸底物,这支持了不同物种的 TER 彼此高度相似的观点,并且可能来自同源基因座。最后,来自芸薹科的不同物种的 TERT 蛋白能够在体内互补功能丧失的 tert 突变体,表明其他物种的 TERT 具有识别拟南芥天然 TER 的能力。最后,我们通过 RNA-seq 免疫沉淀端粒酶复合物并鉴定相关 RNA。利用我们的进化数据,我们将分析限制在芸薹科内保守的、含有模板结构域的 RNA。这些分析揭示了一个高度表达的基因座,其通过 T-DNA 的破坏导致类似于其他端粒酶核心蛋白缺失的端粒表型,表明该 RNA 在端粒维持中具有重要功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fe8/7145096/ec9acde234dc/pone.0222687.g001.jpg

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