Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus

Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus
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DOI:
10.1128/jvi.74.7.3082-3092.2000
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发表时间:
2000-04-01
影响因子:
5.4
通讯作者:
Farrell, PJ
Farrell, PJ
中科院分区:
医学2区
文献类型:
--
作者:
Smith, PR;de Jesus, O;Farrell, PJ

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CST(BART BARF 0)家族病毒RNA在几种类型的EB病毒(EBV)感染中表达,包括EBV相关癌症。这些RNA的许多不同的剪接形式已经被描述;在这里,我们已经澄清了一些更丰富的剪接模式的结构。我们报告的第一个cDNA代表全长CST mRNA从克隆库,并进一步表征转录开始。剪接模式的相对丰度和开放阅读框(ORF)的基因组分析表明,除了研究较多的BARF 0 ORF外,可能存在由CST RNA中的一些上游ORF产生的重要产物。确定了其中两种的潜在生物学功能。RPMS 1 ORF的产物显示为可结合Notch信号转导的CBF 1组分的核蛋白。RPMS 1可抑制NotchIC或EBNA-2通过CBF 1诱导的转录激活。另一个CST ORF A73的蛋白产物显示为可以与细胞RACK 1蛋白相互作用的细胞质蛋白。由于RACK 1调节来自蛋白激酶C和Src酪氨酸激酶的信号,因此结果表明CST产物在生长控制中可能起作用,这可能与癌症如鼻咽癌中CST RNA的大量转录一致。
CST (BART BARF0) family viral RNAs are expressed in several types of Epstein-Barr virus (EBV) infection, including EBV-associated cancers. Many different spliced forms of these RNAs have been described; here we have clarified the structures of some of the more abundant splicing patterns. We report the first cDNAs representing a full-length CST mRNA from a clone library and further characterize the transcription start. The relative abundance of splicing patterns and genomic analysis of the open reading frames (ORFs) suggest that, in addition to the much studied BARF0 ORF, there may be important products made from some of the upstream ORFs in the CST RNAs. Potential biological functions are identified for two of these. The product of the RPMS1 ORF is shown to be a nuclear protein that can bind to the CBF1 component of Notch signal transduction. RPMS1 can inhibit the transcription activation induced through CBF1 by NotchIC or EBNA-2. The protein product of another CST ORF, A73, is shown to be a cytoplasmic protein which can interact with the cell RACK1 protein. Since RACK1 modulates signaling from protein kinase C and Src tyrosine kinases, the results suggest a possible role for CST products in growth control, perhaps consistent with the abundant transcription of CST RNAs in cancers such as nasopharyngeal carcinoma.