Loss of MicroRNA Targets in the 3′ Untranslated Region as a Mechanism of Retroviral Insertional Activation of Growth Factor Independence 1
Loss of MicroRNA Targets in the 3′ Untranslated Region as a Mechanism of Retroviral Insertional Activation of Growth Factor Independence 1
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DOI：
10.1128/jvi.00427-09
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发表时间：
2009-08-15
影响因子：
5.4
通讯作者：
Pedersen, Finn Skou
中科院分区：
文献类型：
--
作者：
Dabrowska, Magdalena Julia;Dybkaer, Karen;Pedersen, Finn Skou
非致癌基因携带逆转录病毒SL 3 -3小鼠白血病病毒在NMRI近交系（NMRI-i）小鼠中诱导严格意义上的T细胞淋巴瘤，平均潜伏期为2至4个月。通过逆转录病毒标签的高通量测序，我们已经确定了携带转录抑制因子和癌基因生长因子独立性1（Gfi 1）的基因组区域作为NMRI-1小鼠基因组中SL 3 -3的常见靶点。在Gfi 1基因的3'非翻译区（3' UTR）的1 kb窗口内鉴定了24个SL 3 -3插入，这是该淋巴瘤模型特有的聚类模式。表达分析确定Gfi 1基因被SL 3 -3插入物转录激活，并且检测到在Gfi 1 3 'UTR中具有插入物的肿瘤的Gfi 1蛋白表达上调。在这里，我们提供的数据支持的机制，逆转录病毒插入Gfi 1的3 'UTR去耦microRNA介导的转录后调控。
The non-oncogene-bearing retrovirus SL3-3 murine leukemia virus induces strictly T-cell lymphomas with a mean latency of 2 to 4 months in mice of the NMRI-inbred (NMRI-i) strain. By high-throughput sequencing of retroviral tags, we have identified the genomic region carrying the transcriptional repressor and oncogene growth factor independence 1 (Gfi1) as a frequent target for SL3-3 in the NMRI-i mouse genome. Twenty-four SL3-3 insertions were identified within a 1-kb window of the 3' untranslated region (3'UTR) of the Gfi1 gene, a clustering pattern unique for this lymphoma model. Expression analysis determined that the Gfi1 gene was transcriptionally activated by SL3-3 insertions, and an upregulation of Gfi1 protein expression was detected for tumors harboring insertions in the Gfi1 3'UTR. Here we provide data in support of a mechanism by which retroviral insertions in the Gfi1 3'UTR decouple microRNA-mediated posttranscriptional regulation.