Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution
Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution
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DOI：
10.1038/s42003-020-0849-9
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发表时间：
2020-03-13
影响因子：
5.9
通讯作者：
Matthews, David A.
中科院分区：
文献类型：
--
作者：
Donovan-Banfield, I'ah;Turnell, Andrew S.;Matthews, David A.
病毒基因组具有高基因密度和复杂的转录策略，使得通过短读RNA-seq方法进行转录组分析成为问题。腺病毒的转录和剪接特别复杂。我们使用长读直接RNA测序来研究腺病毒在感染过程中的转录和剪接。这揭示了一个以前未被认识到的复杂性的选择性剪接和潜在的二级起始密码子的使用。此外，我们发现，大多数病毒转录往往缩短多聚腺苷酸化长度感染的进展。以开放阅读框架为中心的生物信息学分析管道的开发提供了对腺病毒遗传潜力的更深入的定量和定性理解。在整个病毒基因组中，腺病毒产生多个不同的剪接转录物，编码相同的蛋白质。在整个病毒基因组中记录了超过11，000种不同的剪接模式，大多数发生在低水平。这种低水平的选择性剪接模式的使用可能使病毒能够在进化的时间尺度上最大限度地发挥其编码潜力。Donovan-Banfield等人进行了直接RNA长读序测序，以了解人类5型腺病毒感染期间转录和剪接的动态变化。他们发现，在三个时间点上，病毒基因组中的可变剪接模式的组成性低水平使用，这表明病毒策略可以最大限度地发挥其编码潜力
Viral genomes have high gene densities and complex transcription strategies rendering transcriptome analysis through short-read RNA-seq approaches problematic. Adenovirus transcription and splicing is especially complex. We used long-read direct RNA sequencing to study adenovirus transcription and splicing during infection. This revealed a previously unappreciated complexity of alternative splicing and potential for secondary initiating codon usage. Moreover, we find that most viral transcripts tend to shorten polyadenylation lengths as infection progresses. Development of an open reading frame centric bioinformatics analysis pipeline provided a deeper quantitative and qualitative understanding of adenovirus's genetic potential. Across the viral genome adenovirus makes multiple distinctly spliced transcripts that code for the same protein. Over 11,000 different splicing patterns were recorded across the viral genome, most occurring at low levels. This low-level use of alternative splicing patterns potentially enables the virus to maximise its coding potential over evolutionary timescales.Donovan-Banfield et al. perform direct RNA long-read sequencing to understand dynamic changes in transcription and splicing during a human adenovirus type 5 infection. They find constitutive low-level use of alternative splicing patterns across the viral genome over three time points, suggesting a viral strategy to maximize its coding potential