Patterns of RNA Editing in Newcastle Disease Virus Infections.

Patterns of RNA Editing in Newcastle Disease Virus Infections.
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DOI:
10.3390/v12111249
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发表时间:
2020-11-02
期刊:
Viruses
影响因子:
--
通讯作者:
Ferretti L
Ferretti L
中科院分区:
其他
文献类型:
--
作者:
Jadhav A;Zhao L;Ledda A;Liu W;Ding C;Nair V;Ferretti L

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新城疫病毒(NDV)感染中辅助非结构蛋白V和W的表达依赖于RNA编辑。这些蛋白是通过在mRNA中共转录插入一个或两个鸟嘌呤而产生的P蛋白编码序列的帧移位而产生的。但是,可以以较低的频率插入较多的鸟嘌呤。我们分析了来自体外和体内NDV感染样本的深度RNA测序数据,以揭示NDV中mRNA编辑的模式。一个简单的聚合酶口吃的马尔可夫模型很好地描述了插入的分布,为30年前Kolakofsky及其合作者假设的分子过程提供了强有力的定量证实。我们的研究结果表明,新冠病毒聚合酶最初发生阻滞的概率约为0.45,后续插入的概率为0.3。后一种可能性与先前的插入次数、宿主细胞和病毒株大致无关。然而,在LaSota感染中,我们也观察到根据该模型预测的V/W比约为3:1的偏差,这可能归因于与该口吃模型的偏差或W蛋白丰度下调的进一步机制。
The expression of accessory non-structural proteins V and W in Newcastle disease virus (NDV) infections depends on RNA editing. These proteins are derived from frameshifts of the sequence coding for the P protein via co-transcriptional insertion of one or two guanines in the mRNA. However, a larger number of guanines can be inserted with lower frequencies. We analysed data from deep RNA sequencing of samples from in vitro and in vivo NDV infections to uncover the patterns of mRNA editing in NDV. The distribution of insertions is well described by a simple Markov model of polymerase stuttering, providing strong quantitative confirmation of the molecular process hypothesised by Kolakofsky and collaborators three decades ago. Our results suggest that the probability that the NDV polymerase would stutter is about 0.45 initially, and 0.3 for further subsequent insertions. The latter probability is approximately independent of the number of previous insertions, the host cell, and viral strain. However, in LaSota infections, we also observe deviations from the predicted V/W ratio of about 3:1 according to this model, which could be attributed to deviations from this stuttering model or to further mechanisms downregulating the abundance of W protein.
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