Retrovirus-derived RTL5 and RTL6 genes are novel constituents of the innate immune system in the eutherian brain.
Masahito IrieJohbu ItohAyumi MatsuzawaMasahito IkawaHiroshi KiyonariMiho KiharaToru SuzukiYuichi HiraokaFumitoshi IshinoTomoko Kaneko-IshinoPublished in: Development (Cambridge, England) (2022)
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. This article has an associated 'The people behind the papers' interview.
Keyphrases
- immune response
- inflammatory response
- genome wide
- dna methylation
- bioinformatics analysis
- gene expression
- genome wide identification
- poor prognosis
- dendritic cells
- transcription factor
- type diabetes
- subarachnoid hemorrhage
- blood brain barrier
- adipose tissue
- mass spectrometry
- long non coding rna
- skeletal muscle
- spinal cord injury
- single molecule
- circulating tumor
- cerebrospinal fluid
- sensitive detection
- tandem mass spectrometry
- nucleic acid
- fluorescent probe