Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses.
Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses.
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DOI：
10.1371/journal.ppat.1010401
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发表时间：
2022-04
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
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多瘤病毒（PyV）是普遍存在的病原体，可引起毁灭性的人类疾病。由于其基因组的小尺寸，PyV利用复杂的RNA剪接模式来最大化其编码能力。尽管PyV对人类疾病的重要性，但其转录组结构的特征很差。在这里，我们比较了来自8个人类和非人类PyV的短读和长读RNA测序数据。我们提供了BK多瘤病毒（BKPyV），一种重要的人类病原体，和原型PyV，猿猴病毒40（SV40）的详细转录组图谱。我们在PyV中鉴定了普遍的环绕转录，其中转录贯穿polyA位点并多次环绕基因组。比较分析确定新的，保守的转录，增加PyV的编码能力。这些保守的转录本之一编码superT，一种含有两个RB结合LxCxE基序的T抗原。我们发现，superT编码的转录本是丰富的PyV相关的人类癌症。总之，我们表明，比较转录组学的方法可以大大扩展已知的转录本和编码能力，在一个最简单的和最充分研究的病毒家族。多瘤病毒（PyV）是一种小的双链DNA病毒，可引起毁灭性的人类疾病。尽管PyV的临床相关性，在感染过程中由PyV产生的转录本的全部分类的特征很差。我们使用长读段和短读段RNA测序（RNAseq）方法来极大地扩展人类病原体BK多瘤病毒（BKPyV）和原型PyV猿猴病毒40（SV40）的已知转录本多样性。由于PyV含有环状基因组，在转录过程中，宿主RNA聚合酶可以在称为环绕转录的过程中多次环绕基因组。我们发现环绕转录在PyV中广泛保守，并产生不同的早期和晚期RNA。我们使用来自8个PyV的短读RNAseq来鉴定编码新基因产物的保守但以前未注释的转录本。这些转录本之一编码superT，一种含有两个RB结合LxCxE基序的T抗原。我们发现superT在PyV相关的人类癌症中表达。总之，这项工作扩展了我们对PyV转录组的了解，并确定了与人类疾病潜在相关的新转录本。
Polyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized. Here, we compare short- and long-read RNA sequencing data from eight human and non-human PyV. We provide a detailed transcriptome atlas for BK polyomavirus (BKPyV), an important human pathogen, and the prototype PyV, simian virus 40 (SV40). We identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. Comparative analyses identify novel, conserved transcripts that increase PyV coding capacity. One of these conserved transcripts encodes superT, a T antigen containing two RB-binding LxCxE motifs. We find that superT-encoding transcripts are abundant in PyV-associated human cancers. Together, we show that comparative transcriptomic approaches can greatly expand known transcript and coding capacity in one of the simplest and most well-studied viral families. Polyomaviruses (PyV) are small, double-stranded DNA viruses that cause devastating human diseases. Despite the clinical relevance of PyV, the full assortment of transcripts generated by PyV during infection is poorly characterized. We used long- and short-read RNA sequencing (RNAseq) approaches to greatly expand known transcript diversity of the human pathogen BK polyomavirus (BKPyV) and the prototype PyV simian virus 40 (SV40). Because PyV contain circular genomes, during transcription the host RNA polymerase can circle the genome multiple times in a process called wraparound transcription. We find that wraparound transcription is widely conserved across PyV and generates diverse early and late RNAs. We use short-read RNAseq from eight PyV to identify conserved but previously unannotated transcripts encoding novel gene products. One of these transcripts encodes superT, a T antigen that contains two RB-binding LxCxE motifs. We find that superT is expressed in PyV-associated human cancers. Together, this work expands our knowledge of PyV transcriptomes and identifies novel transcripts of potential relevance to human disease.
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影响因子：
4.6
作者：
Keller MW;Rambo-Martin BL;Wilson MM;Ridenour CA;Shepard SS;Stark TJ;Neuhaus EB;Dugan VG;Wentworth DE;Barnes JR
通讯作者：
Barnes JR
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
DOI：
10.1038/nrmicro2992
发表时间：
2013-04
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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影响因子：
5.4
作者：
KAMEN, R;FAVALORO, J;PARKER, J
通讯作者：
PARKER, J
影响因子：
6.4
作者：
Assetta, Benedetta;De Cecco, Marco;Atwood, Walter J.
通讯作者：
Atwood, Walter J.