Retrovirus-derived acquired genes, RTL5 and RTL6, are novel constituents of the innate immune system in the eutherian brain.
Retrovirus-derived acquired genes, RTL5 and RTL6, are novel constituents of the innate immune system in the eutherian brain.
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逆转录病毒衍生的获得性基因 RTL5 和 RTL6 是真兽类大脑先天免疫系统的新组成部分。
DOI：
10.1101/2021.12.29.474483
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Ishino F and Kaneko-Isihno T.
中科院分区：
文献类型：
--
作者：
Irie M;Ithoh J. Matsuzawa A;Ikawa M;Suzuki Y;Hiraoka Y;Ishino F and Kaneko-Isihno T.
逆转录转座子Gag-like 5（RTL 5，也称为sushi-ichi相关反转录转座子同源物8（SIRH 8））和RTL 6（akaSIRH 3）是真兽特有的基因，推测它们来源于逆转录病毒，在遗传学上彼此相关，RTL 5编码强酸性蛋白，RTL 6编码极碱性蛋白，前者在真兽中高度保守，后者在真兽中高度保守，表明它们作为获得性基因的独特和至关重要的作用。在这里，我们报告说，RTL 5和RTL 6是小胶质细胞基因发挥作用的大脑先天性免疫反应的前线对不同的病原体。Venus和mCherry基因敲入小鼠在小胶质细胞中表达RTL 5-mCherry和RTL 6-Venus融合蛋白，并在中枢神经系统（CNS）中表达为细胞外颗粒，并对脂多糖（LPS）等病原体表现出快速反应。、双链（ds）RNA类似物和非甲基化CpG DNA。这些蛋白质将病原体捕获在小胶质细胞中的各种RTL-病原体复合物中，这取决于病原体。这些结果表明，RTL 5和RTL 6发挥功能的影响，对不同的有害物质合作和/或独立保护发育和/或成熟的大脑。这提供了逆转录病毒衍生基因在真兽脑先天免疫系统中发挥作用的第一个证据。
Retrotransposon Gag-like 5 (RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)) andRTL6(akaSIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other.RTL5encodes a strongly acidic protein whileRTL6encodes an extremely basic protein, and the former is well conserved and the latter extremely well conserved among the eutherians, indicating their unique and critically important roles as acquired genes. Here we report thatRTL5andRTL6are microglial genes playing roles in the front line of brain innate immune responses against distinct pathogens. Venus and mCherry knock-in mice exhibited expression of RTL5-mCherry and RTL6-Venus fusion proteins in microglia and as extracellular granules in the central nervus system (CNS), and displayed a rapid response to pathogens such as lipopolysaccharide (LPS), double-stranded (ds) RNA analog and non-methylated CpG DNA. These proteins trapped pathogens in microglia in a variety of RTL-pathogen complexes depending on the pathogens. These results demonstrate thatRTL5andRTL6exert functional effects against different hazardous substances cooperatively and/or independently to protect the developing and/or mature brain. This provides the first evidence that retrovirus-derived genes play a role in the innate immune system of the eutherian brain.