Kruse Konstantin, Nettling Martin, Wappler Nadine, Emmer Alexander, Kornhuber Malte, Staege Martin S, Grosse Ivo
Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle, Germany.
Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
Front Microbiol. 2018 Nov 5;9:2384. doi: 10.3389/fmicb.2018.02384. eCollection 2018.
More than eight percent of the human genome consists of human endogenous retroviruses (HERVs). Typically, the expression of HERVs is repressed, but varying activities of HERVs have been observed in diseases ranging from cancer to neuro-degeneration. Such activities can include the transcription of HERV-derived open reading frames, which can be translated into proteins. However, as a consequence of mutations that disrupt open reading frames, most HERV-like sequences have lost their protein-coding capacity. Nevertheless, these loci can still influence the expression of adjacent genes and, hence, mediate biological effects. Here, we present WebHERV (http://calypso.informatik.uni-halle.de/WebHERV/), a web server that enables the computational prediction of active HERV-like sequences in the human genome based on a comparison of genome coordinates of expressed sequences uploaded by the user and genome coordinates of HERV-like sequences stored in the specialized key-value store DRUMS. Using WebHERV, we predicted putative candidates of active HERV-like sequences in Hodgkin lymphoma (HL) cell lines, validated one of them by a modified SMART (switching mechanism at 5' end of RNA template) technique, and identified a new alternative transcription start site for cytochrome P450, family 4, subfamily Z, polypeptide 1 (CYP4Z1).
超过8%的人类基因组由人类内源性逆转录病毒(HERV)组成。通常情况下,HERV的表达受到抑制,但在从癌症到神经退行性疾病等多种疾病中都观察到了HERV的不同活性。这些活性可能包括HERV衍生的开放阅读框的转录,这些转录本可以被翻译成蛋白质。然而,由于破坏开放阅读框的突变,大多数HERV样序列已经失去了它们的蛋白质编码能力。尽管如此,这些基因座仍然可以影响相邻基因的表达,从而介导生物学效应。在这里,我们展示了WebHERV(http://calypso.informatik.uni-halle.de/WebHERV/),这是一个网络服务器,它能够根据用户上传的表达序列的基因组坐标与存储在专门的键值存储DRUMS中的HERV样序列的基因组坐标进行比较,对人类基因组中活跃的HERV样序列进行计算预测。使用WebHERV,我们预测了霍奇金淋巴瘤(HL)细胞系中活跃的HERV样序列的推定候选物,通过改良的SMART(RNA模板5'端的切换机制)技术验证了其中一个,并确定了细胞色素P450 4家族Z亚家族多肽1(CYP4Z1)的一个新的替代转录起始位点。