2022 Fiscal Year Final Research Report
Mechenism of mammalian specific retrotransposon-derived genes in brain
| Project/Area Number |
17K07243
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Genome biology
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Keywords | レトロトランスポゾン/ウイルス由来遺伝子 / RTL/SIRH genes / 哺乳類特異的遺伝子 / Rtl6/Sirh3 / 脳 / 自然免疫 / ミクログリア / LPS |
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| Outline of Final Research Achievements |
We have demonstrated that retrovirus-derived Rtl6/Sirh3 gene play an important role in the brain innate immune system via its function against bacteria. Rtl6/Sirh3 is one of most conserved genes in eutherians, however, its presumably important function remained elusive for long time. We turned out that RTL6/SIRH3 protein is expressed in microglia and play an essential role to trap a most dangerous bacterial toxin, lipopolysaccharide, as secreted protein in the brain. The fact that a retrovirus-derived gene plays against bacterial infection in the eutherian brain, indicating among the conserved Toll-like receptor (TLR) system in animal kingdom, this eutherian-specific novel constituent plays an important role against bacteria in TLR independent manner, implying that eutherian innate immune system have evolved via acquisition of retrovirus-derived gene(s).
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| Free Research Field |
ゲノム生物学
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトを含む哺乳類のゲノムには、機能不明のレトロウイルス由来の遺伝子が３０以上存在する。本研究のRTL6/SIRH3遺伝子が脳の自然免疫で、細菌感染に対する防御に機能していることを解明し、レトロウイルス由来の遺伝子が細菌感染防御に機能するという、全く予想できなかった事実が明らかになった。これは、Toll-like receptorシステムが動き出す前に、独自に機能していると考えられ、哺乳類の自然免疫系の進化を世界で初めて示したものである。進化における生物とウイルスの関係に新たな知見を与えたものであるだけでなく、将来、脳疾患の原因解明にもつながることが期待される。
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