Georgiou Ioannis, Noutsopoulos Dimitrios, Dimitriadou Eftychia, Markopoulos Georgios, Apergi Anastasia, Lazaros Leandros, Vaxevanoglou Terpsi, Pantos Kostas, Syrrou Maria, Tzavaras Theodore
Laboratory of Reproductive Genetics, Medical School, University of Ioannina, Ioannina, Greece.
Hum Mol Genet. 2009 Apr 1;18(7):1221-8. doi: 10.1093/hmg/ddp022. Epub 2009 Jan 15.
Although human diseases of retrotransposition-derived etiology have been documented, retrotransposon RNA expression and the occurrence of retrotransposition events in the human oocyte are not studied. We investigated the RNA expression of L1 and HERV-K10 retrotransposons in human oocytes by RT-PCR analysis with designed primers. Using denucleated germinal vesicles (GVs), we detected RT-PCR products of expressed L1, HERV-K10 and, unexpectedly, SINE-R, VNTR and Alu (SVA) retrotransposons. Their transcript specificities were identified as such following RNA-FISH and their origin by cloning and sequence alignment analyses. Assessing the expression level in comparison with somatic cells by densitometry analysis, we found that although in normal lymphocytes and transformed HeLa cells their profile was in an order of L1 > HERV-K10 > SVA, remarkably this was reversed in oocytes. To investigate whether de novo retrotransposition events occur and reverse transcriptases are expressed in the human oocyte, we introduced in GVs either a retrotransposition active human L1 or mouse reverse transcriptase deficient-VL30 retrotransposon tagged with an EGFP-based retrotransposition cassette. Interestingly, in both the cases, we observed EGFP-positive oocytes, associated with an abnormal morphology for L1 and granulation for VL30, and the retrotransposition events were confirmed by PCR. Our results: (i) show that L1, HERV-K10 and SVA retrotransposons are transcriptionally expressed and (ii) provide evidence, for the first time, for retrotransposition events occurring in the human oocyte. These findings suggest that both, network of retrotransposon transcripts and controlled retrotranspositions, might serve important functions required for oocyte development and fertilization while the uncontrolled ones might explain the onset of genetic disorders.
虽然已有文献记载了源于逆转座的人类疾病,但尚未对人类卵母细胞中逆转座子RNA的表达及逆转座事件的发生情况进行研究。我们通过使用设计引物进行RT-PCR分析,研究了人类卵母细胞中L1和HERV-K10逆转座子的RNA表达情况。利用去核生发泡(GVs),我们检测到了表达的L1、HERV-K10以及出乎意料的SINE-R、VNTR和Alu(SVA)逆转座子的RT-PCR产物。通过RNA-FISH鉴定了它们的转录本特异性,并通过克隆和序列比对分析确定了其来源。通过密度分析评估与体细胞相比的表达水平,我们发现虽然在正常淋巴细胞和转化的HeLa细胞中它们的表达谱顺序为L1 > HERV-K10 > SVA,但在卵母细胞中情况却明显相反。为了研究人类卵母细胞中是否发生了从头逆转座事件以及是否表达逆转录酶,我们在GVs中引入了带有基于EGFP的逆转座盒标记的具有逆转座活性的人类L1或小鼠逆转录酶缺陷型-VL30逆转座子。有趣的是,在这两种情况下,我们都观察到了EGFP阳性的卵母细胞,L1表现出异常形态,VL30出现颗粒化,并且通过PCR证实了逆转座事件。我们的结果:(i)表明L1、HERV-K10和SVA逆转座子转录表达,(ii)首次为人类卵母细胞中发生的逆转座事件提供了证据。这些发现表明,逆转座子转录本网络和受控的逆转座可能在卵母细胞发育和受精所需的重要功能中发挥作用,而不受控的逆转座可能解释了遗传疾病的发生。