Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes

Although genome-wide polycistronic transcription places major emphasis on post-transcriptional controls in trypanosomatids, messenger RNA cis-regulatory untranslated regions (UTRs) have remained largely uncharacterised. Here, we describe a genome-scale massive parallel reporter assay coupled with 3-UTR-seq profiling in the African trypanosome and identify thousands of regulatory UTRs. Increased translation efficiency was associated with dosage and density of adenine-rich poly-purine tracts (pPuTs). An assessment of synthetic UTRs confirmed the robust correspondence between pPuTs and positive control, as did machine learning based predictions. Those 3-UTRs specifically associated with upregulated expression in bloodstream-stage cells are enriched in both pPuTs and U-rich poly-pyrimidine tracts, suggesting a mechanism for developmental activation through pPuT unmasking. Thus, we describe the UTR sequences that control gene expression in the context of a constitutively transcribed genome and conclude that thousands of UTRs post-transcriptionally reprogram gene expression profiles in trypanosomes.