Immunoprecipitation of RNA-DNA hybrid interacting proteins in Trypanosoma brucei reveals conserved and novel activities, including in the control of surface antigen expression needed for immune evasion by antigenic variation.
Immunoprecipitation of RNA-DNA hybrid interacting proteins in Trypanosoma brucei reveals conserved and novel activities, including in the control of surface antigen expression needed for immune evasion by antigenic variation.
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DOI：
10.1093/nar/gkad836
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发表时间：
2023-11-10
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
RNA-DNA杂交体是基因组的表观遗传特征，其提供了多样化和不断增长的活动范围。通过表征与杂交体相互作用的蛋白质来了解这些功能，但迄今为止所有这些分析都集中在哺乳动物身上，这意味着尚不清楚是否在其他真核生物中发现了类似的RNA-DNA杂交相互作用物谱。非洲锥虫是一种单细胞真核寄生虫的Discoba分组和显示实质性分歧，在几个方面的核心生物学从它的哺乳动物宿主。在这里，我们表明，DNA-RNA杂交免疫沉淀结合质谱回收602个假定的相互作用T。布氏哺乳动物和昆虫感染细胞，一些提供活动也发现在哺乳动物和一些谱系特异性。我们证明，三个因素，两个假定的解旋酶和一个RAD 51蛋白的损失，改变T。布鲁氏菌核RNA-DNA杂交和DNA损伤水平。而且，每个因子的缺失影响了寄生虫免疫存活机制的抗原变异。因此，我们的工作揭示了RNA-DNA杂交体对T.布鲁氏菌生物学，包括宿主免疫逃避中的新功能以及可能对真核基因组功能至关重要的活动。
RNA–DNA hybrids are epigenetic features of genomes that provide a diverse and growing range of activities. Understanding of these functions has been informed by characterising the proteins that interact with the hybrids, but all such analyses have so far focused on mammals, meaning it is unclear if a similar spectrum of RNA–DNA hybrid interactors is found in other eukaryotes. The African trypanosome is a single-cell eukaryotic parasite of the Discoba grouping and displays substantial divergence in several aspects of core biology from its mammalian host. Here, we show that DNA–RNA hybrid immunoprecipitation coupled with mass spectrometry recovers 602 putative interactors in T. brucei mammal- and insect-infective cells, some providing activities also found in mammals and some lineage-specific. We demonstrate that loss of three factors, two putative helicases and a RAD51 paralogue, alters T. brucei nuclear RNA–DNA hybrid and DNA damage levels. Moreover, loss of each factor affects the operation of the parasite immune survival mechanism of antigenic variation. Thus, our work reveals the broad range of activities contributed by RNA–DNA hybrids to T. brucei biology, including new functions in host immune evasion as well as activities likely fundamental to eukaryotic genome function.
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DOI：
10.1016/j.tig.2016.10.002
发表时间：
2016-12
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Chédin F
通讯作者：
Chédin F
影响因子：
28.3
作者：
通讯作者：
--
影响因子：
64.5
作者：
Akiyoshi B;Gull K
通讯作者：
Gull K
DOI：
10.1083/jcb.200902119
发表时间：
2009-07-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Landeira D;Bart JM;Van Tyne D;Navarro M
通讯作者：
Navarro M
影响因子：
16
作者：
Brickner, Joshua R.;Garzon, Jada L.;Cimprich, Karlene A.
通讯作者：
Cimprich, Karlene A.