title: Post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in Trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage-specific regulatory elements.
abstract: 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.
authors.affiliation: Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Mayho
authors.forename: Katelyn
authors.initials: K
authors.lastname: Fenn
authors.forename: Paul
authors.initials: P
authors.lastname: Craddy
authors.forename: Susan
authors.initials: S
authors.lastname: Crosthwaite
authors.forename: Keith
authors.initials: K
authors.lastname: Matthews
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics; D019295:Computational Biology; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D023281:Genomics; D008018:Life Cycle Stages / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development
chemical_list: D020413:3' Untranslated Regions; C406750:EP procyclin protein, Trypanosoma brucei; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D021122:Protein Subunits; D015800:Protozoan Proteins; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D003576:Electron Transport Complex IV