Translational regulation of ATF family members by their upstream open reading frames (uORFs)

Members of the activating transcription factor (ATF) family are stress-induced proteins. ATFs are involved in cell proliferation, survival or apoptosis. Their expression is regulated at both transcriptional and translational levels and may be induced by diverse stress stimuli. Some upstream open reading frames (uORFs) in the 5’ untranslated region (5’ UTR) of the ATF mRNAs have been identified as translational regulators for their downstream open reading frames (ORFs), but the regulatory mechanisms for many of these elements remain unknown. In this thesis, I used dual- luciferase reporter assay to study the regulatory roles of uORFs on the translation of ATFs. All uORFs of ATFs repress downstream ORF translation under normal growth conditions. However, the repressive effect of uORFs can be relieved under specific stress signals. Some common features of uORFs between members of ATF family apparently respond to similar kinds of stress stimuli. On the other hand, our studies uncovered two different signaling pathways that mediate the uORFatf2-regulated translation under UV irradiation.