Characterization of ALTO-encoding circular RNAs expressed by Merkel cell polyomavirus and trichodysplasia spinulosa polyomavirus.
Characterization of ALTO-encoding circular RNAs expressed by Merkel cell polyomavirus and trichodysplasia spinulosa polyomavirus.
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DOI：
10.1371/journal.ppat.1009582
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发表时间：
2021-05
期刊：
影响因子：
6.7
通讯作者：
Wang RC
中科院分区：
文献类型：
--
作者：
Yang R;Lee EE;Kim J;Choi JH;Kolitz E;Chen Y;Crewe C;Salisbury NJH;Scherer PE;Cockerell C;Smith TR;Rosen L;Verlinden L;Galloway DA;Buck CB;Feltkamp MC;Sullivan CS;Wang RC
环状RNA（circRNA）是一类保守的RNA，具有多种功能，包括充当翻译成肽的信使RNA。在这里，我们描述了由人多瘤病毒（HPyVs）产生的环状RNA，其中一些编码先前描述的替代性大T抗原开放阅读框（ALTO）蛋白的变体。环状ALTO RNA（circALTO）可在病毒阳性默克尔细胞癌（VP-MCC）细胞系和肿瘤样品中检测到。CircALTO是稳定的，主要位于细胞质中，并且N6-甲基腺苷（m6 A）被修饰。在培养的细胞中，MCPyV产生的miRNA负调控MCPyV circALTO向ALTO蛋白的翻译。MCPyV ALTO表达在体外增加了一些重组启动子的转录，并上调了先前参与MCPyV发病机制的多个基因的表达。MCPyV circALTO富集在来源于VP-MCC系和circALTO转染的293 T细胞的外泌体中，并且纯化的外泌体可以介导MCPyV阴性细胞中的ALTO表达和转录激活。相关的棘孢发育不良多瘤病毒（TSPyV）也表达可以在感染的组织中检测到的circALTO，并在培养的细胞中产生ALTO蛋白。因此，人多瘤病毒circRNA在人肿瘤和感染的组织中表达，并表达具有调节这些病毒的感染和致瘤性质的潜力的蛋白质。人类多瘤病毒（HPyV）已与包括默克尔细胞癌（MCC）（一种由默克尔细胞多瘤病毒（MCPyV）引起的皮肤癌）和由棘突发育不良多瘤病毒（TSPyV）引起的皮肤和毛发出疹的疾病相关。我们发现HPyVs在受影响的组织中产生单链环状RNA（circRNA）。MCPyV和TSPyV都产生包含早期区域（circALTO）的一部分的circRNA，其可以在培养的细胞中翻译成替代性大T抗原开放阅读框（ALTO）蛋白。先前描述的由MCPyV产生的微小RNA（miRNA）具有抑制ALTO表达的能力。MCPyV circALTO富集在由MCC细胞系和表达circALTO的细胞产生的细胞外囊泡中。最后，我们发现MCPyV ALTO蛋白增强了一些重组启动子的转录，并促进了先前与MCPyV致病相关的多个宿主细胞基因的表达。因此，HPyV产生circRNA，包括被翻译成ALTO蛋白的circALTO，并且MCPyV ALTO具有调节转录的能力。
Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions, including serving as messenger RNAs that are translated into peptides. Here we describe circular RNAs generated by human polyomaviruses (HPyVs), some of which encode variants of the previously described alternative large T antigen open reading frame (ALTO) protein. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N6-methyladenosine (m6A) modified. The translation of MCPyV circALTOs into ALTO protein is negatively regulated by MCPyV-generated miRNAs in cultured cells. MCPyV ALTO expression increases transcription from some recombinant promoters in vitro and upregulates the expression of multiple genes previously implicated in MCPyV pathogenesis. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation in MCPyV-negative cells. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and infected tissues and express proteins that have the potential to modulate the infectious and tumorigenic properties of these viruses. Human polyomaviruses (HPyV) have been linked to diseases including Merkel cell carcinoma (MCC), a skin cancer caused by Merkel cell polyomavirus (MCPyV), and skin and hair eruptions caused by trichodysplasia spinulosa polyomavirus (TSPyV). We discover that HPyVs generate single-stranded, circular RNAs (circRNAs) in affected tissues. Both MCPyV and TSPyV generate circRNAs encompassing part of the early region (circALTOs) that can be translated to the alternative large T antigen open reading frame (ALTO) protein in cultured cells. Previously described microRNAs (miRNAs) generated by MCPyV have the ability to inhibit the expression of ALTO. MCPyV circALTOs are enriched in extracellular vesicles produced by MCC cell lines and cells that express circALTO. Finally, we discover that MCPyV ALTO protein enhances transcription from some recombinant promoters and promotes the expression of multiple host cell genes previously implicated in MCPyV pathogenesis. Thus, HPyVs generate circRNAs, including circALTOs that are translated to ALTO protein, and MCPyV ALTO has the ability to regulate transcription.
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影响因子：
14.9
作者：
Danan M;Schwartz S;Edelheit S;Sorek R
通讯作者：
Sorek R
影响因子：
14.9
作者：
Ho-Xuan H;Glažar P;Latini C;Heizler K;Haase J;Hett R;Anders M;Weichmann F;Bruckmann A;Van den Berg D;Hüttelmaier S;Rajewsky N;Hackl C;Meister G
通讯作者：
Meister G
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
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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