2014 Fiscal Year Annual Research Report
Effects of Runx1-associated lncRNA on asthma pathogenesis
| Project/Area Number |
25860374
|
|---|
| Research Institution | The Institute of Physical and Chemical Research |
|---|
Principal Investigator |
SEO WOOSEOK 独立行政法人理化学研究所, 統合生命医科学研究センター, 国際特別研究員 (40574116)
|
|---|
| Project Period (FY) |
2013-04-01 – 2015-03-31
|
| Keywords | CD4+ T 細胞 / Runx1転写因子 / long non-coding RNA / ヒト喘息疾患発症 |
|---|
| Outline of Annual Research Achievements |
Runx1 protein plays essential functions in blood cell differentiation; however, Runx1 knockout mice also exhibit various autoimmune diseases in addition to defects in hematopoiesis. Indeed, our laboratory showed that Runx1-deficient T cells overexpress IL-4 and this increase in IL-4 production might contribute to the asthma-like pathologies of Runx1 knockout mice.
To investigate whether Runx1 can directly regulate immune responses, I carefully examined Runx1 locus and found that a novel lncRNA (long non-coding RNA) is encoded around Runx1 locus. I found that this lncRNA (Runx1-lncRNA) is expressed unstably and at very low levels, but still showed a helper T cell-biased expression pattern. Interestingly, knockdown of Runx1-lncRNA from helper T lymphocytes in vitro resulted in 2-fold increases in IL-4 expression, suggesting that Runx1-lncRNA might be functionally related to the downstream protein Runx1. For more physiological studies, I generated Runx1-lncRNA knockout mouse line.
Helper T cells from Runx1-lncRNA knockout mice showed around 2-fold increases in IL-4 expression similarly to in vitro knockdown experiments. Moreover, this mouse line also developed asthma-like symptoms, suggesting that Runx1 protein and Runx1-lncRNA might be indeed related. However, detailed analysis of big data genomics in recent public database indicates that this Runx1-lncRNA locus might also contain an transcriptional enhancer. Therefore, further studies are required to delineate the involvement of this potential enhancer and Runx1-lncRNA transcript in the regulation of Runx1 protein function.
|
Research Products
(2 results)
