Lowered Nudix type 5 expression leads to cellular senescence in IMR-90 fibroblast cells

Abstract

The molecule 8-oxo-7,8-dihydroguanine (8-oxoGua), an oxidized form of guanine, can pair with adenine or cytosine during nucleic acid synthesis. RNA sequences that contain 8-oxoGua cause translational errors that lead to the synthesis of abnormal proteins. Human Nudix type 5 (NUDT5), a MutT-related protein, catalyzes the hydrolysis of 8-oxoGDP to 8-oxoGMP, thereby preventing the misincorporation of 8-oxoGua into RNA. To investigate the biological roles of NUDT5 in human fibroblast cells, we established cell lines with decreased levels of NUDT5 expression. In NUDT5 knockdown cells, the RNA oxidation levels were significantly higher, the rates of cellular senescence and cell apoptosis were significantly increased, and the cell viability was significantly decreased in comparison with control cells. These results suggested that the NUDT5 protein could play significant roles in the prevention of RNA oxidation and survival in human fibroblast cells.

Keywords::

• NUDT5
• RNAi
• RNA oxidation
• cellular senescence

Acknowledgments

We are grateful to the members of the Institute of Geriatrics of the Ministry of Health for advice and assistance.

Declaration of interest

The authors declare no conflict of interest. The authors alone are responsible for the content and writing of the article.

This work was supported by the National Natural Science Foundation of China (No. 81171028) and the Key International Science and Technology Cooperation Projects of China (No. 2006DFB31410).