Nucleic Acids Research Advance Access originally published online on September 29, 2006
Nucleic Acids Research 2006 34(18):5312-5324; doi:10.1093/nar/gkl598
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Nucleic Acids Research, 2006, Vol. 34, No. 18 5312-5324
© 2006 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 |
Post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in Trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage-specific regulatory elements
1 Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JT, UK 2 Faculty of Life Sciences, The University of Manchester Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
*To whom correspondence should be addressed. Tel: +44 131 651 3639; Fax: +44 131 651 3670; Email: keith.matthews{at}ed.ac.uk
Received June 14, 2006. Revised July 24, 2006. Accepted August 2, 2006.
Trypanosomes represent an excellent model for the post-transcriptional regulation of gene expression because their genome is organized into polycistronic transcription units. However, few signals governing developmental stage-specific expression have been identified, with there being no compelling evidence for widespread conservation of regulatory motifs. As a tool to search for common regulatory sequences we have used the nuclear-encoded components of the cytochrome oxidase (COX) complex of the trypanosome respiratory chain. Components of this complex represent a form of post-transcriptional operon because trypanosome mitochondrial activity is unusual in being developmentally programmed. By genome analysis we identified the genes for seven components of the COX complex. Each mRNA exhibits bloodstream stage-specific instability, which is not mediated by the RNA silencing pathway but which is alleviated by cycloheximide. Reporter assays have identified regulatory regions within the 3'-untranslated regions of three COX mRNAs operating principally at the translational level, but also via mRNA stability. Interrogation of the mapped regions via oligonucleotide frequency scoring provides evidence for genome-wide conservation of regulatory sequences among a large cohort of procyclic-enriched transcripts. Analysis of the co-regulated subunits of a stage-specific enzyme is therefore a novel approach to uncover cryptic regulatory sequences controlling gene expression at the post-transcriptional level.
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