Transcriptional origin of Kaposi's sarcoma-associated herpesvirus MicroRNAs
Transcriptional origin of Kaposi's sarcoma-associated herpesvirus MicroRNAs
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DOI：
10.1128/jvi.80.5.2234-2242.2006
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发表时间：
2006-03-01
影响因子：
5.4
通讯作者：
Cullen, BR
中科院分区：
文献类型：
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作者：
Cai, XZ;Cullen, BR
卡波西肉瘤相关疱疹病毒(KSHV)编码11个不同的microRNAs，所有这些microRNAs都聚集在KSHV基因组的主要潜伏期相关区域，具有相同的转录方向。由于KSHV的microRNAs都在潜伏感染的细胞中表达，并且基本上不受裂解复制诱导的影响，因此它们可能是从该区域存在的潜在启动子(S)衍生的KSHV转录本中加工出来的。在这里，我们定义了三个潜在的转录本，来自两个不同的KSHV潜在启动子，它们既是KSHV的初级microRNA前体，也是kaposin前mRNAs。这些活动需要通读位于KSHV基因组122070位核苷酸上的一个泄漏的病毒多腺化信号。相反，这种多聚腺苷化信号的识别导致了以前发现的编码KSHV开放阅读框架(ORF)71、72和73蛋白的mRNAs，以及只编码ORF72和ORF71的新的未剪接的KSHV mRNA。因此，起始于KSHV潜伏期相关区域的两个潜在启动子的转录本可能经历两种完全不同的命运，即一方面给出kaposin mRNA和病毒microRNA，要么表达为KSRV ORF71、ORF72或ORF73mRNAs，这取决于位于122070位的病毒多腺化位点是被忽略还是被识别。
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 11 distinct microRNAs, all of which are found clustered within the major latency-associated region of the KSHV genome in the same transcriptional orientation. Because the KSHV microRNAs are all expressed in latently infected cells and are largely unaffected by induction of lytic replication, it appeared probable that they would be processed out of KSHV transcripts that are derived from a latent promoter(s) present in this region. Here, we define three latent transcripts, derived from two distinct KSHV latent promoters, that function as both KSHV primary microRNA precursors and as kaposin pre-mRNAs. These activities require the readthrough of a leaky viral polyadenylation signal located at nucleotide 122070 in the KSHV genome. In contrast, recognition of this polyadenylation signal gives rise to previously identified mRNAs that encode the KSHV open reading frames (ORFs) 71, 72 and 73 proteins as well as a novel unspliced KSHV mRNA that encodes only ORF72 and ORF71. Thus, transcripts initiating at the two latent promoters present in the KSHV latency-associated region can undergo two entirely distinct fates, i.e., processing to give a kaposin mRNA and viral microRNAs on the one hand or expression as KSRV ORF71, ORF72, or ORF73 mRNAs on the other, depending on whether the viral polyadenylation site located at position 122070 is ignored or recognized, respectively.