Identification and analysis of the RNA degrading complexes and machinery of Giardia lamblia using an in silico approach.
Identification and analysis of the RNA degrading complexes and machinery of Giardia lamblia using an in silico approach.
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DOI：
10.1186/1471-2164-12-586
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发表时间：
2011-11-29
期刊：
影响因子：
4.4
通讯作者：
Elmendorf HG
中科院分区：
文献类型：
--
作者：
Williams CW;Elmendorf HG
RNA降解对所有细胞的生存至关重要。随着越来越多的证据表明细胞中普遍存在转录，RNA降解作为一种调控基因表达的手段得到了认可。然而，RNA降解机制只在少数真核生物中得到了广泛的研究，包括酿酒酵母和人类。蓝氏贾第鞭毛虫是一种寄生原生生物，具有不同寻常的基因组特征：它是双核和四倍体，具有非常紧凑的基因组，表现出基因组极简主义的主题，细胞结构通常由数量较少的蛋白质组成，并且拥有大量长的、稳定的、非编码的反义RNA。在这里，我们使用电子计算机方法来研究蓝氏贾第鞭毛虫的主要RNA降解机制，并将其与一系列其他寄生原生生物进行比较。我们已经发现了去烯化和去包裹机制的关键成分以及5‘-3’RNA降解途径的关键成分。我们同样发现，贾第虫体内存在所有主要的3‘-5’RNA降解途径，包括外切体依赖和非外切体依赖的机制。然而，我们观察到RNA降解机制基因的显著丢失，这将导致各种RNA降解途径的蛋白质组成和潜在功能的重要差异。这在外体中最为明显，外体是3‘-5’降解的中心媒介，显然在贾第虫和疟原虫中都含有改变的核心构型，只有四个不同的亚基，而不是典型的六个亚基。此外，贾第鞭毛虫的外切体缺少RRP6、Nab3和Nrd1蛋白，这些蛋白是其他细胞中非编码转录稳定性的关键调节因子。这些发现表明，尽管主要RNA降解机制的完整补充在真核生物进化的早期就存在--并且可能具有功能--但复合体的组成和功能比以前所认识的更具变异性。我们认为，外切体复合体缺失的成分为贾第鞭毛虫不育RNA物种的稳定丰富提供了解释。
RNA degradation is critical to the survival of all cells. With increasing evidence for pervasive transcription in cells, RNA degradation has gained recognition as a means of regulating gene expression. Yet, RNA degradation machinery has been studied extensively in only a few eukaryotic organisms, including Saccharomyces cerevisiae and humans. Giardia lamblia is a parasitic protist with unusual genomic traits: it is binucleated and tetraploid, has a very compact genome, displays a theme of genomic minimalism with cellular machinery commonly comprised of a reduced number of protein components, and has a remarkably large population of long, stable, noncoding, antisense RNAs. Here we use in silico approaches to investigate the major RNA degradation machinery in Giardia lamblia and compare it to a broad array of other parasitic protists. We have found key constituents of the deadenylation and decapping machinery and of the 5'-3' RNA degradation pathway. We have similarly found that all of the major 3'-5' RNA degradation pathways are present in Giardia, including both exosome-dependent and exosome-independent machinery. However, we observe significant loss of RNA degradation machinery genes that will result in important differences in the protein composition, and potentially functionality, of the various RNA degradation pathways. This is most apparent in the exosome, the central mediator of 3'-5' degradation, which apparently contains an altered core configuration in both Giardia and Plasmodium, with only four, instead of the canonical six, distinct subunits. Additionally the exosome in Giardia is missing both the Rrp6, Nab3, and Nrd1 proteins, known to be key regulators of noncoding transcript stability in other cells. These findings suggest that although the full complement of the major RNA degradation mechanisms were present - and likely functional - early in eukaryotic evolution, the composition and function of the complexes is more variable than previously appreciated. We suggest that the missing components of the exosome complex provide an explanation for the stable abundance of sterile RNA species in Giardia.