A pseudouridylation switch in rRNA is implicated in ribosome function during the life cycle of Trypanosoma brucei.
A pseudouridylation switch in rRNA is implicated in ribosome function during the life cycle of Trypanosoma brucei.
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DOI：
10.1038/srep25296
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发表时间：
2016-05-04
影响因子：
4.6
通讯作者：
Michaeli S
中科院分区：
文献类型：
--
作者：
Chikne V;Doniger T;Rajan KS;Bartok O;Eliaz D;Cohen-Chalamish S;Tschudi C;Unger R;Hashem Y;Kadener S;Michaeli S
原生动物寄生虫布氏锥虫会在撒哈拉以南非洲的人和动物中造成毁灭性的疾病，在哺乳动物宿主和以采采蝇为食的媒介之间经历了一个复杂的生命周期。然而，人们对这种寄生虫如何在这样不同的环境中发挥大多数分子功能知之甚少。在这里，我们提供了一个有趣的可能性的证据，即rRNA的假尿路在寄生虫在昆虫中肠和哺乳动物血流之间传递的能力中发挥着重要作用。简单地说，我们用Ψ-SEQ将伪尿苷(Ψ)定位在原环状(PCF)和血流状(BSF)锥体上。我们在由H/Ψ小核仁RNA(SnoRNA)引导的rRNA上检测到68个snoRNA。用HiSeq方法测定了两个生命周期阶段的小RNome，共鉴定出83个H/ACAs。我们观察到，由于指导性snoRNAs水平的增加，bsf中21个ΨS修饰的水平上升。在H69上过表达的snoRNAs指导的修饰在30 °C下对PCF寄生虫提供了轻微的生长优势。有趣的是，这些修饰预计会显著改变大亚基rRNA的二级结构，表明在两个宿主之间的循环过程中，过度修饰的位置可能有助于核糖体功能的适应。
The protozoan parasite Trypanosoma brucei, which causes devastating diseases in humans and animals in sub-Saharan Africa, undergoes a complex life cycle between the mammalian host and the blood-feeding tsetse fly vector. However, little is known about how the parasite performs most molecular functions in such different environments. Here, we provide evidence for the intriguing possibility that pseudouridylation of rRNA plays an important role in the capacity of the parasite to transit between the insect midgut and the mammalian bloodstream. Briefly, we mapped pseudouridines (Ψ) on rRNA by Ψ-seq in procyclic form (PCF) and bloodstream form (BSF) trypanosomes. We detected 68 Ψs on rRNA, which are guided by H/ACA small nucleolar RNAs (snoRNA). The small RNome of both life cycle stages was determined by HiSeq and 83 H/ACAs were identified. We observed an elevation of 21 Ψs modifications in BSF as a result of increased levels of the guiding snoRNAs. Overexpression of snoRNAs guiding modification on H69 provided a slight growth advantage to PCF parasites at 30 °C. Interestingly, these modifications are predicted to significantly alter the secondary structure of the large subunit (LSU) rRNA suggesting that hypermodified positions may contribute to the adaption of ribosome function during cycling between the two hosts.