Origin and evolution of the zinc finger antiviral protein.
Origin and evolution of the zinc finger antiviral protein.
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锌指抗病毒蛋白的起源和进化。
DOI：
10.1371/journal.ppat.1009545
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发表时间：
2021-04
期刊：
影响因子：
6.7
通讯作者：
Bieniasz PD
中科院分区：
文献类型：
--
作者：
Gonçalves-Carneiro D;Takata MA;Ong H;Shilton A;Bieniasz PD
人锌指抗病毒蛋白（ZAP）通过与CpG二核苷酸结合来识别RNA。哺乳动物转录组是CpG贫乏的，ZAP可能已经进化到利用这一特征特异性靶向非自身病毒RNA。系统发育分析表明，ZAP和它的parparaperusPARP 12共享一个祖先基因，出现广泛的真核生物分歧之前，ZAP谱系从PARP 12谱系在四足动物中分歧。值得注意的是，现代真核生物基因组的CpG含量变化很大，ZAP样基因在脊椎动物中出现CpG抑制后出现。人PARP 12对野生型和富含CpG的HIV-1没有表现出抗病毒活性，但来自几种四足动物的ZAP蛋白在人细胞中表达时具有抗病毒活性。在某些情况下，ZAP抗病毒活性需要来自相同或相关物种的TRIM 25蛋白，这表明这些基因的功能共同进化。事实上，在抗病毒活性测定中，ZAP的N-末端结构域中的高变序列有助于物种特异性TRIM 25依赖性。交联免疫沉淀结合RNA测序显示，ZAP蛋白从人类，小鼠，蝙蝠和鳄鱼表现出高度的CpG特异性，而一些鸟类ZAP蛋白出现更混杂。总之，这些数据表明，在某些真核生物谱系中CpG抑制的开始之后，ZAP相关蛋白的富含CpG的RNA指导的抗病毒活性在四足动物中出现，随后是辅因子需求和RNA靶特异性的物种特异性适应。为了控制病毒感染，细胞已经进化出多种机制来检测，修改，有时消除病毒成分。这种机制之一是锌指抗病毒蛋白（ZAP），其结合富含由胞嘧啶和鸟嘌呤组成的元件的RNA序列。病毒RNA的选择只能实现，因为这些元件在人类基因编码的RNA中是稀疏的。在这里，我们追踪了ZAP的分子进化。我们发现，ZAP和一个密切相关的基因，PARP 12，起源于相同的祖先基因存在于脊椎动物和无脊椎动物的前身。我们发现，来自哺乳动物、鸟类和爬行动物的ZAP蛋白具有抗病毒活性，但仅在存在来自同一物种的辅因子TRIM 25的情况下。来自鸟类的ZAP蛋白特别令人感兴趣，因为它们表现出更广泛的抗病毒活性，主要是由对胞嘧啶-鸟嘌呤的宽松需求驱动的。我们的研究结果表明，感染鸟类的病毒是人类疾病的重要载体，它们处于不同的选择压力之下，这种特性可能会影响种间传播的结果。
The human zinc finger antiviral protein (ZAP) recognizes RNA by binding to CpG dinucleotides. Mammalian transcriptomes are CpG-poor, and ZAP may have evolved to exploit this feature to specifically target non-self viral RNA. Phylogenetic analyses reveal that ZAP and its paralogue PARP12 share an ancestral gene that arose prior to extensive eukaryote divergence, and the ZAP lineage diverged from the PARP12 lineage in tetrapods. Notably, the CpG content of modern eukaryote genomes varies widely, and ZAP-like genes arose subsequent to the emergence of CpG-suppression in vertebrates. Human PARP12 exhibited no antiviral activity against wild type and CpG-enriched HIV-1, but ZAP proteins from several tetrapods had antiviral activity when expressed in human cells. In some cases, ZAP antiviral activity required a TRIM25 protein from the same or related species, suggesting functional co-evolution of these genes. Indeed, a hypervariable sequence in the N-terminal domain of ZAP contributed to species-specific TRIM25 dependence in antiviral activity assays. Crosslinking immunoprecipitation coupled with RNA sequencing revealed that ZAP proteins from human, mouse, bat and alligator exhibit a high degree of CpG-specificity, while some avian ZAP proteins appear more promiscuous. Together, these data suggest that the CpG- rich RNA directed antiviral activity of ZAP-related proteins arose in tetrapods, subsequent to the onset of CpG suppression in certain eukaryote lineages, with subsequent species-specific adaptation of cofactor requirements and RNA target specificity. To control viral infections, cells have evolved a variety of mechanisms that detect, modify and sometimes eliminate viral components. One of such mechanism is the Zinc Finger Antiviral Protein (ZAP) which binds RNA sequences that are rich in elements composed of a cytosine followed by a guanine. Selection of viral RNA can only be achieved because such elements are sparse in RNAs encoded by human genes. Here, we traced the molecular evolution of ZAP. We found that ZAP and a closely related gene, PARP12, originated from the same ancestral gene that existed in a predecessor of vertebrates and invertebrates. We found that ZAP proteins from mammals, birds and reptiles have antiviral activity but only in the presence of a co-factor, TRIM25, from the same species. ZAP proteins from birds were particularly interesting since they demonstrated a broader antiviral activity, primarily driven by relaxed requirement for cytosine-guanine. Our findings suggest that viruses that infect birds–which are important vectors for human diseases–are under differential selective pressures and this property may influence the outcome of interspecies transmission.
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影响因子：
15.9
作者：
Meyerson NR;Sawyer SL
通讯作者：
Sawyer SL
影响因子：
6.7
作者：
Greenbaum BD;Levine AJ;Bhanot G;Rabadan R
通讯作者：
Rabadan R
DOI：
10.1038/nrg2719
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
BIRD, AP;TAGGART, MH
通讯作者：
TAGGART, MH
DOI：
10.1016/0045-6039(85)90488-9
发表时间：
1985-01-01
期刊：
CELL DIFFERENTIATION
影响因子：
--
作者：
COOPER, DN;GERBERHUBER, S
通讯作者：
GERBERHUBER, S