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Expression of a human cytomegalovirus late gene is posttranscriptionally regulated by a 3'-end-processing event occurring exclusively late after infection.

机译:人类巨细胞病毒晚期基因的表达在转录后受到仅在感染后晚期发生的3'末端加工事件的调控。

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A phenomenon of posttranscriptional regulation has been previously identified in cytomegalovirus-infected human fibroblast cells (Wathen and Stinski, J. Virol. 41:462, 1982). A region typifying this phenomenon has been located within the large unique component of the viral genome (map units 0.408 to 0.423). Even though this transcriptional unit was highly transcribed at early times after infection, mRNAs from this region were only detectable on the polyribosomes after viral DNA replication. Thus, this region is believed to code for a late gene. Single-strand-specific nuclease mapping experiments of viral transcripts established that the transcriptional initiation sites and the 5' ends of a downstream exon were identical at early and late times. However, the late transcripts differed from the early transcripts by the processing of the 3' end of the viral RNAs. This involved either the removal of a distinct region of the transcript by the selection of an upstream cleavage and polyadenylation site or the differential splicing of the RNA molecule. The upstream cleavage and polyadenylation site was identified by nuclease mapping analyses and DNA sequencing. The 3'-end processing of these transcripts is necessary for the detection of these viral RNAs within the cytoplasm of the infected cell. We propose that human cytomegalovirus either codes for a factor(s) that is involved in the 3'-end-processing event at late times after infection or stimulates the synthesis of a host cell factor(s) involved in this complex regulatory event. This level of regulation may have an influence on the types of cells that permit productive cytomegalovirus replication.
机译:先前已经在巨细胞病毒感染的人成纤维细胞中鉴定了转录后调节的现象(Wathen和Stinski,J.Virol.41:462,1982)。代表这种现象的区域位于病毒基因组的独特大区域内(图单元0.408至0.423)。即使该转录单位在感染后的早期就被高度转录,但在病毒DNA复制后,只能在多核糖体上检测到该区域的mRNA。因此,据信该区域编码晚期基因。病毒转录本的单链特异性核酸酶作图实验确定,转录外显子的转录起始位点和5'末端在早期和晚期是相同的。但是,后期转录本与早期转录本的区别在于病毒RNA 3'末端的加工。这涉及通过选择上游切割和聚腺苷酸化位点去除转录物的独特区域或RNA分子的差异剪接。通过核酸酶作图分析和DNA测序鉴定上游切割和聚腺苷酸化位点。这些转录本的3'末端加工对于检测被感染细胞的细胞质内的这些病毒RNA是必需的。我们建议人类巨细胞病毒或者编码在感染后晚期参与3'-末端加工事件的因素,或者刺激参与此复杂调控事件的宿主细胞因子的合成。这种调节水平可能会影响允许生产性巨细胞病毒复制的细胞类型。

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