Elucidating the role of long non-coding RNA in vivo by genome editing technologies

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: CHIBA Tomoki 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (00645830)
• Research Collaborator: ASAHARA Hiroshi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 長鎖非コードRNA / 炎症性サイトカイン / ゲノム編集

Outline of Final Research Achievements

Recent advantages of transcriptome analyses revealed that non-coding RNAs, especially long non-coding (lnc) RNAs, are transcribed across genome and involved in various aspects of biological processes. I have identified a novel lncRNA that positively regulates inflammatory cytokine expression and named LASC. LASC is required for the expression of inflammatory cytokines such as IL-6 and GM-CSF. Recruitment of transcription factor NF-kB was strongly reduced in LASC deficient cells, suggesting that LASC could regulate inflammatory cytokine expression at transcriptional level. In order to clarify the role of LASC in inflammation in vivo, LASC knockout mice were generated by genome editing technology and showed resistance to endotoxin shock.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ヒトやマウスにおいて、タンパク質をコードしない非コードRNA（non-coding RNA）は20,000種類以上あると推定されている。その多くは機能を持たないRNAであると考えられているが、一部のRNAは生命機能に重要な役割を果たしている。LASCは炎症性サイトカインの発現に重要な長鎖非コードRNAであり、個体における炎症応答に重要なRNAであることが示された。