An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation
An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation
复制标题
隐藏在哺乳动物基因组中的古老逆转录病毒RNA元件及其参与共选逆转录病毒基因调控
DOI：
10.1101/2021.03.02.433518
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发表时间：
2021
期刊：
影响因子：
3.3
通讯作者：
Miyazawa Takayuki
中科院分区：
文献类型：
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作者：
Kitao Koichi;Nakagawa So;Miyazawa Takayuki
背景逆转录病毒利用多种独特的RNA元件来控制RNA的加工和翻译。然而，目前还不清楚内源性逆转录病毒（ERV）中存在哪些功能性RNA元件。从ERVs的基因co-option有时需要的viralcis元件的保护所需的基因表达，这可能会揭示在ERVs.ResultsHere的RNA调节，我们的特点是在ERVs中发现的RNA元件组成的三个特定的序列基序，称为SPRE。SPRE样元件在不同的ERV家族中被发现，但没有在任何外源病毒序列检查。我们在几种哺乳动物基因组中观察到超过一千个SPRE样元件的拷贝;在人类和绒猴基因组中，它们与谱系特异性ERV重叠。SPRE最初发现于人类合胞素-1和2。事实上，几种哺乳动物的合胞素基因：猕猴的mac-syncytin-3、天蚕的syncytin-Ten 1和食肉目的syncytin-Car 1都含有SPRE样元件。报告基因分析表明，SPRE对基因表达的增强依赖于报告基因。SPRE的突变损害了野生型syncytin-2的表达，而相同的突变并不影响密码子优化syncytin-2，这表明SPRE活性依赖于编码sequence.ConclusionsThese结果表明多个独立的入侵各种哺乳动物基因组的逆转录病毒窝藏SPRE样元素。在这些逆转录病毒衍生的几种合胞菌素中发现了功能性SPRE样元件。该元件可促进病毒基因的表达，所述病毒基因由于编码序列内的低效密码子频率或抑制元件而被抑制。这些发现为逆转录病毒中RNA元件的长期进化和基因表达的分子机制提供了新的见解。
BackgroundRetroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viralcis-elements required for gene expression, which might reveal the RNA regulation in ERVs.ResultsHere, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in humansyncytin-1andsyncytin-2. Indeed, several mammaliansyncytingenes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-typesyncytin-2expression while the same mutation did not affect codon-optimizedsyncytin-2, suggesting that SPRE activity depends on the coding sequence.ConclusionsThese results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in severalsyncytingenes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses.