Biology subjects

Ishino, F.

Publications and source records attributed to Ishino, F..

2 recordsLinked to original sources

bioRxiv2021

Retrovirus-derived acquired genes, RTL5 and RTL6, are novel constituents of the innate immune system in the eutherian brain.

Retrotransposon Gag-like 5 (RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)) and RTL6 (aka SIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other. RTL5 encodes a strongly acidic protein while RTL6 encodes 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 that RTL5 and RTL6 are 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 that RTL5 and RTL6 exert 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.

evolutionary biology↗

bioRxiv2021

PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta

The therian-specific gene paternally expressed 10 (Peg10) plays an essential role in placenta formation: Peg10 knockout (KO) mice exhibit early embryonic lethality due to severe placental defects. The PEG10 protein exhibits homology to long terminal repeat (LTR) retrotransposon GAG and POL proteins, therefore mice harboring a mutation in its highly conserved viral aspartic protease motif in the POL-like region were generated because it is essential for LTR retrotransposons/retroviruses. Intriguingly, frequent perinatal lethality, not early embryonic lethality, was observed with fetal and placental growth retardation starting mid-gestation. In the mutant placentas, severe defects were observed in the fetal vasculature, where PEG10 is expressed in the three trophoblast cell layers that surround fetal capillary endothelial cells. Thus, Peg10 has essential roles not only in early placenta formation, but also in placental vasculature maintenance from mid- to late-gestation. This implies that along the feto-maternal placenta interface an interaction occurs between two retrovirus-derived genes, Peg10 and retrotransposon Gag like 1 (Rtl1, also called Peg11), that is essential for the maintenance of fetal capillary endothelial cells. Summary statementDisruption of the highly conserved viral aspartic protease domain in PEG10 causes placental abnormality leading to perinatal lethality in mice.

developmental biology↗