The role of small peptide derived from lncRNA on innate immune responce.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16695
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kumamoto University
• Principal Investigator: kouwaki takahisa 熊本大学, 大学院生命科学研究部(医), 助教 (90780784)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 自然免疫 / long non-coding RNA

Outline of Final Research Achievements

Innate immunity is the first line of defense against viral pathogens. Upon innate immune sensors recognize viruses, interferons and cytokines are elaborate to eliminate the viruses. RIG-I like receptors, cGAS and Toll like receptors detects the viral nucleotides and activate downstream signal cascade. These signals join to the TANK binding kinase 1 (TBK1) and induce Type I interferons. Precisely, TBK1 is essential factor for innate immune responses. Elucidation of the mechanisms of innate immune systems is beneficial to establish newly therapeutic applications. In this study, we identified the small peptide derived from long non-coding RNA (lncRNA) as a binding partner with TBK1. We found that small peptide was generated upon viral infection. Small peptide bound to TBK1. Small peptide stimulates type I interferon promoter activity via TBK1 dependent pathway. Our finding suggest that small peptide derived from lncRNA acts as a type I interferon stimulator along with TBK1 signaling.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

新型コロナウイルスの世界的大流行など、ウイルス感染症の脅威は人類の社会生活に暗い影を落としている。ウイルスに対する自然免疫応答の制御機構の解明は新たな治療法の開発に有益な知見となる。本研究では、自然免疫シグナル伝達分子であるTBK1について研究を行い、TBK1の働きを制御する新規蛋白質として、long non-coding RNAから翻訳された低分子ペプチドを同定した。低分子ペプチドはウイルス感染に応答して翻訳されTBK1を介してインターフェロンの産生を促進していることが明らかとなった。TBK1の未解明の抗ウイルス機構の一端が解明され今後の発展が期待される。