In response to external and internal signals, mammalian cells elicit changes in gene expression patterns that profoundly influence the global cellular response. The transcriptional events that regulate gene expression changes have been thoroughly studied, but less-well understood post-transcriptional processes are emerging as major regulatory mechanisms. Post-transcriptional gene regulation includes pre-mRNA processing and maturation, mRNA transport, stability and translation, as well as protein processing, modification and degradation. We are keenly interested in investigating the mechanisms that regulate the expression of proliferative, cell cycle-regulatory, and stress-response proteins.? Over the past 10 years, this Project has examined mRNAs encoding various stress-response and proliferative proteins. During this funding period, we have focused our attention on mRNAs encoding the hypoxia-inducible factor (HIF)-1 and the MAP Kinase phosphatase (MKP)-1. We have reported that RBPs HuR and PTB associate with HIF-1 mRNA and promote its translation in response to treatment with hypoxia and with the hypoxia mimetic CoCl2. We also reported that the post-transcriptional regulation of MKP-1 expression is mediated by HuR and NF90; both RBPs stabilized the MKP-1 mRNA, although only HuR promoted MKP-1 translation.? Ongoing studies are examining the regulation of HO-1 mRNA expression in response to nitric oxide. This process was found to be robustly regulated by stabilization of the HO-1 mRNA through the association of RBPs.
Showing the most recent 10 out of 80 publications
