chen Address: Kaul Human Genetics Building
Room 440A
720 20th Street South
Birmingham, AL 35294-0024
(205) 934-5073
(205) 934-0758


Dr. Ching-Yi Chen (b. 1963) is an Assistant Professor of Biochemistry and Molecular Genetics. Dr. Chen received his B.S. degree from National Cheng Kung University in Taiwan (1986) and Ph.D. degree from Baylor College of Medicine (1996). He then moved to University of California at San Diego and received his postdoctoral training in the laboratory of Dr. Michael Karin, where he was supported by three consecutive postdoctoral fellowships. He joined the faculty at UAB in 2002.

Lab Research Focus: Mechanism and Regulation of Mammalian mRNA Turnover

Control of mRNA turnover plays an important role in determining levels of gene expression during cell growth, differentiation, and development. One class of cis elements responsible for rapid mRNA decay in mammalian cells is the AU-rich element (ARE), found in the 3' untranslated regions of cytokine, proto-oncogene, and growth factor mRNAs. In addition to their rapid mRNA turnover, these short-lived transcripts are stabilized in response to various extracellular stimuli. Understanding regulation of mRNA turnover would identify dysregulation responsible for the development of disease and would also provide new means to specifically control the expression of specific genes at the posttranscriptional level. Therefore, the research interests of my laboratory are primarily focused on two directions.

  1. Mechanism and regulation of ARE-directed mRNA turnover. Recently, we discovered that the human exosome, a multisubunit particle containing nine exoribonulease, is responsible for rapid degradation of short-lived ARE-containing mRNAs. The rapid turnover of these mRNAs mediated by the exosome requires certain destabilizing ARE-binding proteins (ARE-BPs), previously shown to promote ARE-directed mRNA turnover. These ARE-BPs were found to interact with the exosome and may be responsible for recruiting the exosome to unstable ARE-containing mRNAs, thereby promoting rapid mRNA degradation. We are currently investigating this recruitment-based mechanism. Additional ongoing projects in the laboratory also involve:
  2. to investigate whether the human exosome is involved in rapid degradation of other unstable mRNAs in addition to ARE-containing mRNAs in intact cells using RNA interference (RNAi) techniques and
  3. to functionally and structurally investigate a novel ARE-BP, which we identified and is required for degradation of ARE-containing mRNAs.
  4. Mechanism by which signal transduction pathways stabilize interleukin-2 mRNA in response to T cell activation. We investigate the control of IL-2 mRNA turnover and use it as a model to understand the mechanism of mRNA stabilization in response to extracellular stimuli, which is a relatively unexplored area. The research involves:
  5. to identify the cis elements and trans-acting factors that are responsible for rapid turnover of IL-2 mRNA and
  6. to identify the cis elements and trans-acting factors that are required for stabilization of IL-2 mRNA in response to T cell activation.

Recent Publications
Chen, C. Y., Del Gatto-Konczak, F., Wu, Z., and Karin, M. (1998) Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway. Science 280, 1945-1949.

Chen, C. Y., Gherzi, R., Andersen, J. S., Gaietta, G., J?rchott, K., Royer, H. D., Mann, M., and Karin, M. (2000) Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes & Dev. 14, 1236-1248.

Chen, C. Y., Gherzi, R., Ong, S. E., Chan, E. L., Raijmakers, R., Pruijn, G. J., Stoecklin, G., Moroni, C., Mann, M., and Karin, M. (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107, 451-464.