title: Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development.
abstract: The post-transcriptional control of gene expression is becoming increasingly important in the understanding of regulated events in eukaryotic cells. The parasitic kinetoplastids have a unique reliance on such processes, because their genome is organized into polycistronic transcription units in which adjacent genes are not coordinately regulated. Indeed, the number of RNA-binding proteins predicted to be encoded in the genome of kinetoplastids is unusually large, invoking the presence of unique RNA regulators dedicated to gene expression in these evolutionarily ancient organisms. Here, we report that a small CCCH zinc finger protein, TbZFP3, enhances development between life-cycle stages in Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both with the translational machinery and with other small CCCH proteins previously implicated in trypanosome developmental control. Antibodies to this protein also co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively expressed, it exhibits developmentally regulated association with polyribosomes, and mutational analysis demonstrates that this association is essential for the expression of phenotype. TbZFP3 is therefore a novel regulator of developmental events in kinetoplastids that acts at the level of the post-transcriptional control of gene expression.
authors.affiliation: Institute of Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, King's Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland, United Kingdom.
authors.forename: Athina
authors.initials: A
authors.lastname: Paterou
authors.forename: Pegine
authors.initials: P
authors.lastname: Walrad
authors.forename: Paul
authors.initials: P
authors.lastname: Craddy
authors.forename: Katelyn
authors.initials: K
authors.lastname: Fenn
authors.forename: Keith
authors.initials: K
authors.lastname: Matthews
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004252:DNA Mutational Analysis; D018105:DNA, Kinetoplast / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000737:chemistry; D008969:Molecular Sequence Data; D010641:Phenotype; D011132:Polyribosomes; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry; D012323:RNA Processing, Post-Transcriptional; D012270:Ribosomes / Q000737:chemistry; D014346:Trypanosoma brucei brucei; D016335:Zinc Fingers
chemical_list: D018105:DNA, Kinetoplast; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C053277:procyclic acidic repetitive protein, Trypanosoma