Activation of transcription and retrotransposition of a novel retroelement, Steamer, in neoplastic hemocytes of the mollusk Mya arenaria

Activation of transcription and retrotransposition of a novel retroelement, Steamer, in neoplastic hemocytes of the mollusk Mya arenaria
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DOI:
10.1073/pnas.1409945111
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发表时间:
2014-09-30
影响因子:
11.1
通讯作者:
Goff, Stephen P.
Goff, Stephen P.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arriagada, Gloria;Metzger, Michael J.;Goff, Stephen P.

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北大西洋的双壳类软体动物,最著名的是软壳蛤Mya arenaria,患有一种与白血病非常相似的循环系统传染病。该疾病的特征是血淋巴中具有高有丝分裂指数的胚样细胞的急剧扩增。对患病蛤的血淋巴的检查显示高水平的逆转录酶活性,这是逆转录病毒和逆转录因子的标志。通过对来自血淋巴的RNA进行深度测序,我们鉴定了一种新的逆转录因子的转录本,在此命名为Steamer。该元件的DNA由长末端重复序列标记,并编码与哺乳动物逆转录病毒Gag-Pol蛋白相似的单个大蛋白。Steamer mRNA水平在患病血细胞中特异性升高,并且高表达与疾病状态相关。每个基因组的DNA拷贝数在患病的血细胞中以极高的水平存在,表明广泛的逆转录和逆转录转座。M中的蒸汽机激活。arenaria是一个灾难性的遗传不稳定性诱导的例子,可能引发或促进白血病的进程。
Bivalve mollusks of the North Atlantic, most prominently the soft shell clam Mya arenaria, are afflicted with an epidemic transmissible disease of the circulatory system closely resembling leukemia. The disease is characterized by a dramatic expansion of blast-like cells in the hemolymph with high mitotic index. Examination of hemolymph of diseased clams revealed high levels of reverse transcriptase activity, the hallmark of retroviruses and retroelements. By deep sequencing of RNAs from hemolymph, we identified transcripts of a novel retroelement, here named Steamer. The DNA of the element is marked by long terminal repeats and encodes a single large protein with similarity to mammalian retroviral Gag-Pol proteins. Steamer mRNA levels were specifically elevated in diseased hemocytes, and high expression was correlated with disease status. DNA copy number per genome was present at enormously high levels in diseased hemocytes, indicative of extensive reverse transcription and retrotransposition. Steamer activation in M. arenaria is an example of a catastrophic induction of genetic instability that may initiate or advance the course of leukemia.