Retrovirus-derived RTL5 and RTL6 genes are novel constituents of the innate immune system in the eutherian brain.
Retrovirus-derived RTL5 and RTL6 genes are novel constituents of the innate immune system in the eutherian brain.
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DOI：
10.1242/dev.200976
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发表时间：
2022-09-15
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--
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逆转录转座子Gag样5 [RTL 5，也称为sushi-ichi相关逆转录转座子同源物8（SIRH 8）]和RTL 6（也称为SIRH 3）是真兽亚纲特异性基因，推测来源于逆转录病毒，并且在系统发育上彼此相关。它们分别编码一种强酸性和极碱性蛋白质，并且在真兽目动物中非常保守。在这里，我们报告说，RTL 5和RTL 6是小胶质细胞基因的作用，在先天性脑免疫反应的前线。Venus和mCherry基因敲入小鼠在小胶质细胞中表现出RTL 5-mCherry和RTL 6-Venus融合蛋白的表达，并在中枢神经系统中表现为细胞外点和颗粒。这些蛋白质显示出对病原体如脂多糖（LPS）、双链（ds）RNA类似物和非甲基化CpG DNA的快速反应，协同和/或独立地起作用。使用Rtl 6或Rtl 5敲除小鼠的实验提供了另外的证据，即RTL 6和RTL 5在脑中分别充当针对LPS和dsRNA的因子，首次证明逆转录病毒衍生的基因在真兽类先天免疫系统中发挥作用。最后，我们提出了一个模型，强调胚胎外组织作为逆转录病毒衍生基因的起源位点的重要性。 RTL 5和RTL 6是从脑中小胶质细胞中的逆转录病毒获得的真兽特异性基因。它们在真兽脑免疫系统中的病原体清除中起重要作用。
Retrotransposon Gag-like 5 [RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)] and RTL6 (also known as SIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other. They, respectively, encode a strongly acidic and extremely basic protein, and are well conserved among the eutherians. Here, we report that RTL5 and RTL6 are microglial genes with roles in the front line of innate brain immune response. Venus and mCherry knock-in mice exhibited expression of RTL5-mCherry and RTL6-Venus fusion proteins in microglia and appeared as extracellular dots and granules in the central nervous system. These proteins display a rapid response to pathogens such as lipopolysaccharide (LPS), double-stranded (ds) RNA analog and non-methylated CpG DNA, acting both cooperatively and/or independently. Experiments using Rtl6 or Rtl5 knockout mice provided additional evidence that RTL6 and RTL5 act as factors against LPS and dsRNA, respectively, in the brain, providing the first demonstration that retrovirus-derived genes play a role in the eutherian innate immune system. Finally, we propose a model emphasizing the importance of extra-embryonic tissues as the origin site of retrovirus-derived genes. RTL5 and RTL6 are eutherian-specific genes acquired from a retrovirus in microglia in the brain. They play important roles in pathogen clearance in the eutherian brain immune system.
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影响因子：
2.7
作者：
GOULD, SJ;VRBA, ES
通讯作者：
VRBA, ES
影响因子：
64.5
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Thomson T
影响因子：
64.8
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Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
64.8
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Coorens THH;Oliver TRW;Sanghvi R;Sovio U;Cook E;Vento-Tormo R;Haniffa M;Young MD;Rahbari R;Sebire N;Campbell PJ;Charnock-Jones DS;Smith GCS;Behjati S
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影响因子：
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通讯作者：
Ishino F