A statistical framework for quantifying the nuclear export rate of influenza viral mRNAs

A statistical framework for quantifying the nuclear export rate of influenza viral mRNAs
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量化流感病毒 mRNA 核输出率的统计框架

DOI:
10.1101/2023.04.07.536075
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发表时间:
2023
期刊:
bioRxiv
影响因子:
--
通讯作者:
Mineki Saito
Mineki Saito
中科院分区:
--
文献类型:
--
作者:
Michi Miura;Naho Kiuchi;Siu-Ying Lau;Bobo Wing-Yee Mok;Hiroshi Ushirogawa;Tadasuke Naito;Honglin Chen;Mineki Saito

文献摘要

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甲型流感病毒感染时,从八个片段的病毒基因组转录病毒mRNAs。病毒转录的动力学,病毒转录物的核输出,以及它们在八个片段之间的潜在变异,都没有得到很好的描述。在这里,我们介绍了一个统计框架,用于从原位mRNA定位的快照中估计每个片段的核出口速率。这利用了基于成像的原位转录组分析观察到的单个时间点的细胞到细胞的变化。利用我们的模型,我们揭示了八个病毒片段的mRNA核输出率的变化。值得注意的是,两种流感病毒抗原血凝素和神经氨酸酶是核输出中最慢的部分,这表明甲型流感病毒可能利用病毒转录物的核保留来推迟抗原分子的表达。我们在这项研究中提出的框架可以广泛地用于研究转录爆发中产生的新生转录本的核保留。
Influenza A virus transcribes viral mRNAs from the eight segmented viral genome when it infects. The kinetics of viral transcription, nuclear export of viral transcripts, and their potential variation between the eight segments are poorly characterised. Here, we introduce a statistical framework for estimating the nuclear export rate of each segment from a snapshot of in situ mRNA localisation. This exploits the cell-to-cell variation at a single time point observed by an imaging-based in situ transcriptome assay. Using our model, we revealed the variation in the mRNA nuclear export rate of the eight viral segments. Notably, the two influenza viral antigens hemagglutinin and neuraminidase were the slowest segments in the nuclear export, suggesting the possibility that influenza A virus uses the nuclear retention of viral transcripts to delay the expression of antigenic molecules. Our framework presented in this study can be widely used for investigating the nuclear retention of nascent transcripts produced in a transcription burst.