Role of post-transcriptional regulation in cellular senescence

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: SUGIMOTO Masataka 独立行政法人国立長寿医療研究センター, 老化細胞研究プロジェクトチーム, プロジェクトリーダー (50426491)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 細胞老化 / RNA結合タンパク質 / HuR

Outline of Final Research Achievements

Upon stress, cells undergo irreversible growth arrest called cellular senescence. Cellular senescence acts as potent anti-tumor barrier, and recent observations suggest it is also involved in aging-associated disorders. Numerous studies have been performed to elucidate the mechanisms regulating senescence, but little is known about how post-transcriptional regulation contributes to it. In this study, we focused on the role of HuR in cellular senescence.
HuR level declined during cellular senescence. HuR knockdown induced senescence with concomitant expression of ARF protein. In addition, these cells show several senescence-associated features including the induction of cytokine induction. Moreover, adipose-specific deletion of HuR gene induced senescence in early age, which is accompanied by reduced insulin sensitivity. Together, these findings demonstrate HuR-mediated post-transcriptional regulation plays essential roles in the induction and maintenance of senescence phenotypes.

Free Research Field

細胞生物学