Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei.

Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei.
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哺乳动物病原体布氏锥虫中小非编码RNA上假尿苷RNA修饰的鉴定和功能意义。

DOI:
10.1016/j.jbc.2022.102141
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发表时间:
2022-07
影响因子:
4.8
通讯作者:
Michaeli, Shulamit
Michaeli, Shulamit
中科院分区:
生物学2区
文献类型:
--
作者:
Rajan, K. Shanmugha;Adler, Katerina;Doniger, Tirza;Cohen-Chalamish, Smadar;Aharon-Hefetz, Noa;Aryal, Saurav;Pilpel, Yitzhak;Tschudi, Christian;Unger, Ron;Michaeli, Shulamit

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引起昏睡病的布氏锥虫在昆虫和哺乳动物宿主之间循环。然而,RNA修饰如假尿苷化对其在这两种不同宿主环境中存活能力的影响尚不清楚。在这里,两个全基因组的方法被应用于定位小核仁RNA(snoRNA),7SL RNA,穹窿RNA,和来自布氏锥虫的tRNA上的假尿苷酸化位点(pseudouridinylation sites,pADs)。我们使用HydraPsiSeq和RiboMeth-seq表明,引导2′-O-甲基化的核糖体C/D snoRNA增加了对其靶rRNA的引导修饰的效率。我们发现,这些非编码RNA在寄生虫的两个生命阶段(昆虫宿主和哺乳动物宿主)的差异水平的bifos。此外,tRNA异构体丰度和tRNA修饰的特点是在这两个生命阶段,证明阶段特异性调节。我们的结论是,这里确定的差异性的rRNA修饰可能有助于调节非编码RNA的功能,参与rRNA加工,rRNA修饰,蛋白质合成,和蛋白质易位在循环的寄生虫之间的两个主机。
Trypanosoma brucei, the parasite that causes sleeping sickness, cycles between an insect and a mammalian host. However, the effect of RNA modifications such as pseudouridinylation on its ability to survive in these two different host environments is unclear. Here, two genome-wide approaches were applied for mapping pseudouridinylation sites (Ψs) on small nucleolar RNA (snoRNA), 7SL RNA, vault RNA, and tRNAs from T. brucei. We show using HydraPsiSeq and RiboMeth-seq that the Ψ on C/D snoRNA guiding 2′-O-methylation increased the efficiency of the guided modification on its target, rRNA. We found differential levels of Ψs on these noncoding RNAs in the two life stages (insect host and mammalian host) of the parasite. Furthermore, tRNA isoform abundance and Ψ modifications were characterized in these two life stages demonstrating stage-specific regulation. We conclude that the differential Ψ modifications identified here may contribute to modulating the function of noncoding RNAs involved in rRNA processing, rRNA modification, protein synthesis, and protein translocation during cycling of the parasite between its two hosts.
DOI: 10.1074/jbc.m209215200
发表时间: 2003-05-16
影响因子: 4.8
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