Nucleic Acids Research Advance Access originally published online on February 14, 2008
Nucleic Acids Research 2008 36(6):2024-2031; doi:10.1093/nar/gkn027
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Nucleic Acids Research, 2008, Vol. 36, No. 6 2024-2031
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Oxygen-dependent, alternative promoter controls translation of tco1+ in fission yeast
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
*To whom correspondence should be addressed. Tel: +1 443 287 5026; Fax: +1 410 955 4129; Email: peter.espenshade{at}jhmi.edu
Received November 5, 2007. Revised January 15, 2008. Accepted January 16, 2008.
Eukaryotic cells respond to changes in environmental oxygen supply by increasing transcription and subsequent translation of gene products required for adaptation to low oxygen. In fission yeast, the ortholog of mammalian sterol regulatory element binding protein (SREBP), called Sre1, activates low-oxygen gene expression and is essential for anaerobic growth. Previous studies in multiple organisms indicate that SREBP transcription factors function as positive regulators of gene expression by increasing transcription. Here, we describe a unique mechanism by which activation of Sre1-dependent transcription downregulates protein expression under low oxygen. Paradoxically, Sre1 inhibits expression of tco1+ gene product by activating its transcription. Under low oxygen, Sre1 directs transcription of tco1+ from an alternate, upstream promoter and inhibits expression of the normoxic tco1+ transcript. The resulting low-oxygen transcript contains an additional 751 nt in the 5' untranslated region that is predicted to form a stable, complex secondary structure. Interestingly, polysome profile experiments revealed that this new longer transcript is translationally silent, leading to a decrease in Tco1 protein expression under low oxygen. Together, these results describe a new mechanism for oxygen-dependent control of gene expression and provide an example of negative regulation of protein expression by an SREBP homolog.