Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8397, Japan.
Int J Mol Sci. 2019 Jun 13;20(12):2875. doi: 10.3390/ijms20122875.
Endogenous retroelements constitute almost half of the mammalian genome. Given that more than 60% of human genomic bases are transcribed, transcripts containing these retroelements may impact various biological processes. However, the physiological roles of most retroelement-containing transcripts are yet to be revealed. Here, we profiled the expression of retroelement-containing human transcripts during vaccination and found that vaccination upregulated transcripts containing only particular retroelements, such as the MLT-int element of endogenous retroviruses. MLT-int-containing transcripts were distributed mainly in the nucleus, suggesting their unique roles in the nucleus. Furthermore, we demonstrated that MLT-int RNA suppressed interferon promoter activity in the absence of immune stimuli. Based on these lines of evidence, we speculate a model of a role of the previously unnoticed MLT-int element in preventing excess innate immune activation after elimination of immune stimuli. Our results may emphasize the importance of retroelement-containing transcripts in maintaining host immune homeostasis.
内源性反转录元件构成了哺乳动物基因组的近一半。鉴于超过 60%的人类基因组碱基被转录,包含这些反转录元件的转录本可能会影响各种生物过程。然而,大多数包含反转录元件的转录本的生理作用尚未被揭示。在这里,我们对疫苗接种过程中包含内源性逆转录病毒 MLT-int 元件等特定反转录元件的人类转录本的表达进行了分析,发现疫苗接种会上调这些转录本的表达。这些包含 MLT-int 的转录本主要分布在细胞核中,表明它们在细胞核中具有独特的作用。此外,我们证明了 MLT-int RNA 在没有免疫刺激的情况下抑制干扰素启动子活性。基于这些证据,我们推测了一个此前未被注意到的 MLT-int 元件在消除免疫刺激后防止固有免疫过度激活的作用模型。我们的研究结果可能强调了包含反转录元件的转录本在维持宿主免疫平衡中的重要性。